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bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Obesity and age are risk factors for feline diabetes. This study aimed to test the hypothesis that age, long-term obesity, and dietary composition would lead to peripheral and hepatorenal insulin resistance, indicated by higher endogenous glucose production (EGP) in the fasted and postprandial state, higher blood glucose and insulin, and higher leptin, free thyroxine, and lower adiponectin concentrations. Using triple tracer-(2)H(2)O, [U-(13)C(3)] propionate, and [3,4-(13)C(2)] glucose infusion, and indirect calorimetry-we investigated carbohydrate and fat metabolic pathways in overnight-fasted neutered cats (13 young lean, 12 old lean, and 12 old obese), each fed three different diets (high protein with and without polyunsaturated fatty acids, and high carbohydrate) in a crossover design. EGP was lowest in fasted and postprandial obese cats despite peripheral insulin resistance, indicated by hyperinsulinemia. Gluconeogenesis was the most important pathway for EGP in all groups, but glycogen contributed significantly. Insulin and leptin concentrations were higher in old than in young lean cats; adiponectin was lowest in obese cats but surprisingly highest in lean old cats. Diet had little effect on metabolic parameters. [HYP] We conclude that hepatorenal insulin resistance does not develop in the fasted or postprandial state, even in long-term obese cats , allowing the maintenance of euglycemia through lowering EGP .
OUTPUT: | entailment | 0 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Obesity is a risk factor for developing inflammatory bowel disease. Pea is unique with its high content of dietary fiber, polyphenolics, and glycoproteins, all of which are known to be health beneficial. We aimed to investigate the impact of green pea (GP) supplementation on the susceptibility of high-fat diet (HFD)-fed mice to dextran sulfate sodium (DSS)-induced colitis. Six-week-old C57BL/6J female mice were fed a 45% HFD or HFD supplemented with 10% GP. After 7-week dietary supplementation, colitis was induced by adding 2.5% DSS in drinking water for 7 days followed by a 7-day recovery period. GP supplementation ameliorated the disease activity index score in HFD-fed mice during the recovery stage, and reduced neutrophil infiltration, mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and inflammatory markers interleukin (IL)-6, cyclooxygenase-2 (COX-2), IL-17, interferon-γ (IFN-γ), and inducible nitric oxide synthase (iNOS) in HFD-fed mice. Further, GP supplementation increased mucin 2 content and mRNA expression of goblet cell differentiation markers including Trefoil factor 3 (Tff3), Krüppel-like factor 4 (Klf4), and SAM pointed domain ETS factor 1 (Spdef1) in HFD-fed mice. In addition, GP ameliorated endoplasmic reticulum (ER) stress as indicated by the reduced expression of Activating transcription factor-6 (ATF-6) protein and its target genes chaperone protein glucose-regulated protein 78 (Grp78), the CCAAT-enhancer-binding protein homologous protein (CHOP), the ER degradation-enhancing α-mannosidase-like 1 protein (Edem1), and the X-box binding protein 1 (Xbp1) in HFD-fed mice. [HYP] In conclusion, GP supplementation ameliorated the severity of DSS -induced colitis in HFD-fed mice, which was associated with the suppression of inflammation, mucin depletion, and ER stress in the colon.
OUTPUT: | entailment | 1 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] LY2881835 is a selective, potent, and efficacious GPR40 agonist. The objective of the studies described here was to examine the pharmacological properties of LY2881835 in preclinical models of T2D. Significant increases in insulin secretion were detected when LY2881835 was tested in primary islets from WT mice but not in islets from GPR40 KO mice. Furthermore, LY2881835 potentiated glucose stimulated insulin secretion in normal lean mice. Acute administration of LY2881835 lowered glucose during OGTTs in WT mice but not in GPR40 KO mice. These findings demonstrate that LY2881835 induces GPR40-mediated activity ex vivo and in vivo. LY2881835 was administered orally at 10 mg/kg to diet-induced obese (DIO) mice (an early model of T2D due to insulin resistance) for 14 days. Statistically significant reductions in glucose were seen during OGTTs performed on days 1 and 15. When a study was done for 3 weeks in Zucker fa/fa rats, a rat model of insulin resistance, normalization of blood glucose levels equivalent to those seen in lean rats was observed. A similar study was performed in streptozotocin (STZ)-treated DIO mice to explore glucose control in a late model of T2D. In this model, pancreatic insulin content was reduced ~80% due to STZ-treatment plus the mice were insulin resistant due to their high fat diet. Glucose AUCs were significantly reduced during OGTTs done on days 1, 7, and 14 compared to control mice. [HYP] In conclusion, these results demonstrate that LY2881835 functions as a GPR40 -specific insulin secretagogue mediating immediate and durable glucose control in rodent models of early- and late-stage T2D.
OUTPUT: | entailment | 2 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] To elucidate the acute metabolic actions of insulin-like growth factor I (IGF-I), we administered a primed (250 micrograms/kg), continuous (5 micrograms/kg.min) infusion of human recombinant (Thr 59) IGF-I or saline to awake, chronically catheterized 24-h fasted rats for 90 min. IGF-I was also infused while maintaining euglycemia (glucose clamp technique) and its effects were compared to those of insulin. IGF-I infusion caused a twofold rise in IGF-I levels and a 75-85% decrease in plasma insulin. When IGF-I alone was given, plasma glucose fell by 30-40 mg/dl (P less than 0.005) due to a transient twofold increase (P less than 0.05) in glucose uptake; hepatic glucose production and plasma FFA levels remained unchanged. IGF-I infusion with maintenance of euglycemia produced a sustained rise in glucose uptake and a marked stimulation of [3-3H]glucose incorporation into tissue glycogen, but still failed to suppress glucose production and FFA levels. IGF-I also produced a generalized 30-40% reduction in plasma amino acids, regardless of whether or not hypoglycemia was prevented. This was associated with a decrease in leucine flux and a decline in the incorporation of [1-14C]leucine into muscle and liver protein (P less than 0.05). When insulin was infused in a dosage that mimicked the rise in glucose uptake seen with IGF-I, nearly identical changes in amino acid metabolism occurred. However, insulin suppressed glucose production by 65% and FFA levels by 40% (P less than 0.001). Furthermore, insulin was less effective than IGF-I in promoting glycogen synthesis. [HYP] We conclude that (a) IGFBPs produces hypoglycemia by selectively enhancing glucose uptake; (b) IGFBPs is relatively ineffective in suppressing hepatic glucose production or FFA levels; and (c) IGFBPs , like insulin, lowers circulating amino acids by reducing protein breakdown rather than by stimulating protein synthesis.
OUTPUT: | contradiction | 3 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Hyperglycemia was reported to enhance angiotensin (Ang) II generation in rat cardiomyocytes, and Ang II inhibition reduces cardiovascular morbidity and mortality in diabetic patients. In diabetic patients, the enhanced activation of intracellular pathways related with myocyte hypertrophy and gene expression might enhance the progression of cardiac damage. Therefore, we investigated the effects of glucose on Ang II-mediated activation of Janus-activated kinase (JAK)-2, a tyrosine kinase related with myocyte hypertrophy and cytokine and fibrogenetic growth factor overexpression, in ventricular myocytes isolated from nonfailing human hearts (n = 5) and failing human hearts (n = 8). In nonfailing myocytes, JAK2 phosphorylation was enhanced by Ang II only in the presence of high glucose (25 mmol/l) via Ang II type I (AT1) receptors (+79% vs. normal glucose, P < 0.05). JAK2 activation was prevented by inhibitors of reactive oxygen species (ROS) generation (diphenyleneiodonium [DPI], tiron, and apocynin). In myocytes isolated from failing hearts, JAK2 phosphorylation was enhanced by high glucose alone (+107%, P < 0.05). High glucose-induced JAK2 activation was blunted by both ACE inhibition (100 nmol/l ramipril) and AT1 antagonism (1 mumol/l valsartan), thus revealing that the effects are mediated by autocrine Ang II production. Inhibition of ROS generation also prevented high glucose-induced JAK2 phosphorylation. [HYP] In conclusion, in human nonfailing myocytes, high glucose allows Ang II to activate JAK2 signaling, whereas in failing myocytes, hyperglycemia alone is able to induce Ang II generation, which in turn activates JAK2 via enhanced oxidative stress.
OUTPUT: | entailment | 4 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] The effect of peritonitis on peritoneal membrane solute transport characteristics was determined as part of a multicenter study in children on continuous ambulatory/cycling peritoneal dialysis. Ninety-three children each underwent a 4-h peritoneal equilibration test (PET) with 1,100 ml/m2 2.5% Dianeal for determination of mass transfer area coefficients (MTAC), dialysate to plasma ratios (D/P) for creatinine and urea at 0, 30, 60, 120, 180, and 240 min and dialysate glucose levels at 0, 30, 60, 120, 180, and 240 min for calculation of D/Do. The mean age of the study cohort was 10.1 +/- 5.6 years (range 0.1-19 years). There were 162 historical episodes of peritonitis; at the time of the PET tests, 36 children had never had an episode of peritonitis (group I) while 57 children had a history of one or more episodes of peritonitis (group II). In group II children, the 4-h glucose D/Do was significantly lower and the 4-h D/P creatinine ratio, the creatinine MTAC, and the glucose MTAC were significantly higher (each P < 0.05) than in group I. In children with a history of peritonitis caused by Gram-negative organisms, the 4-h glucose D/Do (P < 0.05) and the creatinine MTAC (P < 0.05) were significantly lower and the glucose MTAC (P = 0.07) nearly significantly lower than in children without a history of peritonitis. Linear regression analysis did not demonstrate a correlation between any of the variables and duration of peritoneal dialysis, while the rate of peritonitis was weakly correlated with glucose MTAC (r = 0.34, P < 0.05) and with 4-h glucose D/Do (r = -0.222, P < 0.01). [HYP] We conclude that children with a history of peritonitis have peritoneal membranes that are more permeable to glucose and creatinine than children without a history of peritonitis , and that the peritoneal membranes of children who have had peritonitis caused by Gram -negative organisms are also more permeable to creatinine and glucose.
OUTPUT: | entailment | 5 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] The liver X receptors (LXRs) play a key role in cholesterol and bile acid metabolism but are also important regulators of glucose metabolism. Recently, LXRs have been proposed as a glucose sensor affecting LXR-dependent gene expression. We challenged wild-type (WT) and LXRαβ(-/-) mice with a normal diet (ND) or a high-carbohydrate diet (HCD). Magnetic resonance imaging showed different fat distribution between WT and LXRαβ(-/-) mice. Surprisingly, gonadal (GL) adipocyte volume decreased on HCD compared with ND in WT mice, whereas it slightly increased in LXRαβ(-/-) mice. Interestingly, insulin-stimulated lipogenesis of isolated GL fat cells was reduced on HCD compared with ND in LXRαβ(-/-) mice, whereas no changes were observed in WT mice. Net de novo lipogenesis (DNL) calculated from Vo(2) and Vco(2) was significantly higher in LXRαβ(-/-) than in WT mice on HCD. Histology of HCD-fed livers showed hepatic steatosis in WT mice but not in LXRαβ(-/-) mice. Glucose tolerance was not different between groups, but insulin sensitivity was decreased by the HCD in WT but not in LXRαβ(-/-) mice. Finally, gene expression analysis of adipose tissue showed induced expression of genes involved in DNL in LXRαβ(-/-) mice compared with WT animals as opposed to the liver, where expression of DNL genes was repressed in LXRαβ(-/-) mice. [HYP] We thus conclude that absence of DNL stimulates LXRs in adipose tissue, but suppresses LXRs in the liver, demonstrating opposite roles of LXR in LXRs regulation in these two tissues.
OUTPUT: | contradiction | 6 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] This study investigated the effect of aldose reductase (AR) inhibitors on hypertension in diabetes. Diabetes was induced with streptozotocin, while AR inhibitors zopolrestat and ferulic acid were administered at 2 weeks after streptozotocin treatment and for 6 weeks afterwards. Then, blood pressure (BP) and serum level of glucose were determined. Concentration-response curves for phenylephrine (PE), KCl, and acetylcholine (ACh) were obtained in isolated aorta. In addition, ACh-induced NO and reactive oxygen species (ROS) generation in aorta and histopathology were examined. Compared with the control animals, diabetes increased diastolic and systolic BP. AR inhibitors reduced diastolic BP elevation without affecting the developed hyperglycaemia. Diabetes increased the contractile response of aorta to KCl, and decreased the relaxation response to Ach, while administering AR inhibitors prevented an impaired response to ACh. Incubation of aorta isolated from diabetic animals with AR inhibitors did not affect the impaired relaxation response to ACh. In addition, AR inhibitors negated the impaired Ach-stimulated NO generation seen in aorta isolated from diabetic animals. Furthermore, diabetes was accompanied with marked infiltration of leukocytes in aortic adventitia, endothelial cell pyknosis, and increased ROS formation. AR inhibitors reduced leukocyte infiltration and inhibited endothelial pyknosis and ROS formation. [HYP] In conclusion, AR inhibitors negate diabetes-evoked hypertension via ameliorating impaired endothelial relaxation and NO production.
OUTPUT: | entailment | 7 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. [HYP] Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia.
OUTPUT: | entailment | 8 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Diabetes mellitus (DM) is characterized by alterations in fluid balance and blood volume homeostasis. Renal interstitial hydrostatic pressure (RIHP) has been shown to play a critical role in mediating sodium and water excretion under various conditions. The objective of this study was to determine the effects of immediate and delayed initiation of insulin treatment on the restoration of the relationship between RIHP, natriuretic, and diuretic responses to acute saline volume expansion (VE) in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body wt). Four groups of female Sprague-Dawley rats were studied: normal control group (C), untreated diabetic group (D), immediate insulin-treated diabetic group (DI; treatment with insulin for 2 wk was initiated immediately when diabetes was confirmed, which was 2 days after STZ injection), and delayed insulin-treated diabetic group (DDI; treatment with insulin for 2 wk was initiated 2 wk after STZ injection). RIHP and sodium and water excretions were measured before and during VE (5% body wt/30 min) in the four groups of anesthetized rats. VE significantly increased RIHP, fractional excretion of sodium (FE(Na)), and urine flow rate (V) in all groups of rats. Basal RIHP, RIHP response to VE (Delta RIHP), and FE(Na) and V responses to VE (Delta FE(Na) and Delta V) were significantly lower in the D group compared with the C group of rats. Delta RIHP was significantly higher in both DI and DDI groups compared with D group but was similar to that of the C group of rats. While in the DI group the Delta FE(Na) response to VE was restored, Delta FE(Na) was significantly increased in DDI compared with D group, but it remained lower than that of the C group. [HYP] In conclusion, 5-HT1 receptor subtype treatment initiated immediately after the onset of diabetes restores basal RIHP and RIHP , natriuretic, and diuretic responses to VE; however, delayed 5-HT1 receptor subtype treatment restores the basal RIHP and RIHP response to VE but does not fully restore the natriuretic response to VE.
OUTPUT: | contradiction | 9 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] In pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia and hypoxemia progressively worsen during the third trimester, which increases circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block) at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced β-cell responsiveness in fetuses with PI-induced intrauterine growth restriction (IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater compared with age-matched controls, but the levels were similar to near-term controls. Therefore, our objective was to determine whether elevations in plasma NE concentrations inhibit insulin secretion and produce compensatory β-cell responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-stimulated insulin secretion (GPAIS) conditions in the absence and presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus than in controls, but fetal weights were not different. PI fetuses had lower (P < 0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1 and insulin concentrations and greater plasma NE concentrations (891 ± 211 v. 292 ± 65 pg/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in controls (0.34 ± 0.03 v. 1.08 ± 0.06 ng/ml; P < 0.05). ADR-block increased GSIS in PI fetuses (1.19 ± 0.11 ng/ml; P < 0.05) but decreased GSIS in controls (0.86 ± 0.02 ng/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses but not in controls. Insulin content per islet was not different between treatments. [HYP] We conclude that elevations in fetal plasma NE suppress insulin concentrations, and that compensatory β-cell stimulus-secretion responsiveness is present before IUGR.
OUTPUT: | entailment | 10 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Monolayer cultures of neonatal rat pancreatic cells were examined to ascertain whether they synthesize prostaglandin E (PGE) and to determine the effects on insulin secretion caused by PGE and drugs that inhibit its synthesis. PGE release into the medium was observed. Sodium salicylate and ibuprofen (at drug concentrations similar to those achieved therapeutically in humans in vivo) inhibited PGE synthesis in a dose-responsive fashion to a maximum of 70-80% inhibition. Inhibition of PGE synthesis was accompanied by augmented insulin secretion. Both PGE synthesis inhibitors shifted the glucose dose-insulin response curves to the left at low glucose concentrations and augmented maximal insulin release at high glucose concentrations. Increments in glucose-induced insulin secretion induced by sodium salicylate correlated well (r = 0.89) with inhibition of PGE synthesis and addition of exogenous PGE1 to the cultures reversed the augmenting effects of the drug on insulin secretion. [HYP] It is concluded that cultures of pancreatic cells synthesize PGE and that a function of PGE in these cultures appears to be a tonic negative modulation of glucose -induced insulin secretion .
OUTPUT: | entailment | 11 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] Methodology for assessing the glycolytic and oxidative fluxes from plasma glucose, by measuring 3H2O and 14CO2 rates of production during [3-3H]- and [U-14C]glucose infusion, was tested in healthy subjects. In study 1, during staircase 3H2O infusion in six subjects, calculated rates of 3H2O appearance agreed closely with 3H2O infusion rates. In study 2, when [2-3H]glucose and NaH14CO3 were infused in four subjects in the basal state and during a 4-h euglycemic insulin (approximately 70 microU/ml) clamp, accurate estimates of the rates of [2-3H]glucose detritiation were obtained (94-97% of the expected values), and the recovery factor of NaH14CO3 did not change during hyperinsulinemia. In study 3, 11 subjects underwent a 4-h euglycemic insulin (approximately 70 microU/ml) clamp with [3-3H]- and [U-14C]glucose infusion and measurement of gaseous exchanges by indirect calorimetry to estimate the rates of total glycolysis, glycogen synthesis, glucose oxidation, nonoxidative glycolysis, hepatic glucose production, glucose recycling, and glucose conversion to fat. Hyperinsulinemia stimulated glycogen synthesis above baseline more than glycolysis [increment of 4.78 +/- 0.37 vs. 2.0 +/- 0.17 mg.min-1 x kg-1 of lean body mass (LBM), respectively, P < 0.01] and incompletely suppressed (approximately 87%) hepatic glucose production. The major component of nonoxidative glycolysis shifted from glucose recycling in the postabsorptive state (approximately 57% of nonoxidative glycolysis) to glucose conversion to fat during hyperinsulinemia (approximately 59% of nonoxidative glycolysis). Lipid oxidation during the insulin clamp was negatively correlated with both isotopic glucose oxidation (r = -0.822, P < 0.002) and glycolysis (r = -0.582, P < 0.07). [HYP] In conclusion, in healthy subjects, glycogen synthesis plays a greater role than glycolysis and glucose oxidation in determining insulin -mediated glucose disposal.
OUTPUT: | entailment | 12 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] Glutamate is generated during nutrient stimulation of pancreatic islets and has been proposed to act both as an intra- and extra-cellular messenger molecule. We demonstrate that glutamate is not co-secreted with the hormones from intact islets or purified α- and β-cells. Fractional glutamate release was 5-50 times higher than hormone secretion. Furthermore, various hormone secretagogues did not elicit glutamate efflux. Interestingly, epinephrine even decreased glutamate release while increasing glucagon secretion. Rather than being co-secreted with hormones, we show that glutamate is mainly released via plasma membrane excitatory amino acid transporters (EAAT) by uptake reversal. Transcripts for EAAT1, 2 and 3 were present in both rat α- and β-cells. Inhibition of EAATs by L-trans-pyrrolidine-2,4-dicarboxylate augmented intra-cellular glutamate and α-ketoglutarate contents and potentiated glucose-stimulated insulin secretion from islets and purified β-cells without affecting glucagon secretion from α-cells. [HYP] In conclusion, intra-cellular glutamate-derived metabolite pools are linked to glucose -stimulated insulin but not glucagon secretion.
OUTPUT: | entailment | 13 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). [HYP] In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH -induced myocardial ischemia-reperfusion damages in OSA patients.
OUTPUT: | entailment | 14 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here we studied young-adult PlGF-deficient (PlGF(-/-)) and wild-type mice on a high-fat diet in the nongravid state and at embryonic day (E) 13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF(-/-) pregnancies. PlGF(-/-) mice showed altered intraadipose dynamics, with the following: 1) less blood vessels and fewer brown, uncoupling protein (UCP)-1-positive, adipocytes in white sc and perigonadal fat compartments and 2) white adipocyte hypertrophy. The mRNA expression of beta(3)-adrenergic receptors, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and UCP-1 was decreased accordingly. Moreover, PlGF(-/-) mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF(-/-) and wild-type dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (vascular endothelial growth factor receptor-1, peroxisome proliferator-activated receptor-gamma(2)) and thermogenesis (beta(3)-adrenergic receptors, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and UCP-1) genes was down-regulated; circulating insulin levels gradually increased during pregnancy. [HYP] In conclusion, reduced adipose vascularization in PlGF(-/-) mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia .
OUTPUT: | entailment | 15 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] Munc13-1 is a diacylglycerol (DAG) receptor that is essential for synaptic vesicle priming. We recently showed that Munc13-1 is expressed in rodent and human islet beta-cells and that its levels are reduced in islets of type 2 diabetic humans and rat models, suggesting that Munc13-1 deficiency contributes to the abnormal insulin secretion in diabetes. To unequivocally demonstrate the role of Munc13-1 in insulin secretion, we studied heterozygous Munc13-1 knockout mice (+/-), which exhibited elevated glucose levels during intraperitoneal glucose tolerance tests with corresponding lower serum insulin levels. Munc13-1(+/-) mice exhibited normal insulin tolerance, indicating that a primary islet beta-cell secretory defect is the major cause of their hyperglycemia. Consistently, glucose-stimulated insulin secretion was reduced 50% in isolated Munc13-1(+/-) islets and was only partially rescued by phorbol ester potentiation. The corresponding alterations were minor in mice expressing one allele of a Munc13-1 mutant variant, which does not bind DAG (H567K/+). Capacitance measurements of Munc13-1(+/-) and Munc13-1(H567k/+) islet beta-cells revealed defects in granule priming, including the initial size and refilling of the releasable pools, which become accentuated by phorbol ester potentiation. [HYP] We conclude that Munc13-1 plays an important role in glucose -stimulated insulin secretion and that Munc13-1 deficiency in the pancreatic islets as occurs in diabetes can reduce insulin secretion sufficient to cause abnormal glucose homeostasis.
OUTPUT: | entailment | 16 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Peptide YY (PYY) has been shown to inhibit stimulated insulin secretion under in vivo conditions in the mouse, the rat, and the dog. In the present study, we investigated the effects of PYY on insulin secretion from the isolated perfused rat pancreas and isolated rat islets. In isolated pancreas perfused in presence of 8.3 mM glucose, PYY at 10(-10) and 10(-9) M, but not at 10(-8) M, inhibited insulin secretion. In the presence of 5.5 mM glucose, PYY (10(-9) M) did not modify basal insulin release but reduced the biphasic insulin response to arginine (10 mM). PYY also markedly reduced the pancreatic vascular flow rate; this effect was observed at all three concentrations tested in a dose-dependent manner. [HYP] In isolated islets, glucose (15 mM)-stimulated PYY was inhibited by insulin secretion at 10(-7) M. We conclude that in the perfused rat pancreas, insulin secretion inhibits PYY and induces vasoconstriction without a causal relationship.
OUTPUT: | contradiction | 17 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Adipose tissue is a complex endocrine organ which coordinates several crucial biological functions including fatty acid metabolism, glucose metabolism, energy homeostasis, and immune function. Brown adipose tissue (BAT) is most abundant in young infants during the brain growth spurt when demands for omega-3 docosahexaenoic acid (DHA, 22:6n-3) is greatest for brain structure. Our aim was to characterize relative biosynthesis of omega-3 long chain polyunsaturated fatty acids (LCPUFA) from precursors in cultured white (WAT) and brown (BAT) cells and study relevant gene expression. Mouse WAT and BAT cells were grown in regular DMEM media to confluence, and differentiation was induced. At days 0 and 8 cells were treated with albumin bound d5-18:3n-3 (d5-ALA) and analyzed 24h later. d5-ALA increased cellular eicosapentaenoic acid (EPA, 20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) in undifferentiated BAT cells, whereas differentiated BAT cells accumulated 20:4n-3, EPA and DPA. DHA as a fraction of total omega-3 LCPUFA was greatest in differentiated BAT cells compared to undifferentiated cells. Undifferentiated WAT cells accumulated EPA, whereas differentiated cells accumulated DPA. WAT accumulated trace newly synthesized DHA. Zic1 a classical brown marker and Prdm16 a key driver of brown fat cell fate are expressed only in BAT cells. Ppargc1a is 15 fold higher in differentiated BAT cells. [HYP] We conclude that in differentiated adipose cells accumulating fat, BAT cells but not WAT cells synthesize DHA , supporting the hypothesis that BAT is a net producer of DHA .
OUTPUT: | entailment | 18 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] The present study examined the effect of 5-hydroxytraptamine (5-HT) on the feeding behavior of transgenic mice with neuropeptide Y (NPY) overexpression. Solution of 5-HT (1, 2.5 or 5 mg/kg) was administered intraperitoneally into (1) NPY-overexpressing mice, and (2) wild-type mice with 2-deoxy-d-glucose (2-DG) induced hyperphagia. The NPY-overexpressing mice were further divided into five groups: (1) control mice, (2) mice treated with 5-HT (5 mg/kg), (3) mice treated with 5-HT (5 mg/kg) and ketanserin (0.5 or 1 mg/kg), a 5-HT2A receptor antagonist, (4) mice treated with insulin (1 IU/kg), and (5) mice treated with insulin (1 IU/kg) and 5-HT (5 mg/kg). Food intake and plasma glucose levels were measured. The results showed that 5-HT reduced hyperphagia in both NPY-overexpressing mice and 2-DG-treated mice in dose-dependent manner. Hyperglycemia was induced by 5-HT administration. Ketanserin antagonized the 5-HT induced hypophagia and hyperglycemia. Insulin, on the other hand, prevented 5-HT induced hyperglycemia but not the hypophagic effect. [HYP] In conclusion, 5-HT reduces hyperphagia in the NPY-overexpressing rat through action on 5-HT 2A receptors and this hypophagic effect of 5-HT does not depend on the hyperglycemia.
OUTPUT: | entailment | 19 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes vasodilation independent of insulin. We examined the effect of GLP-1 on muscle microvasculature and glucose uptake. After confirming that GLP-1 potently stimulates nitric oxide (NO) synthase (NOS) phosphorylation in endothelial cells, overnight-fasted adult male rats received continuous GLP-1 infusion (30 pmol/kg/min) for 2 h plus or minus NOS inhibition. Muscle microvascular blood volume (MBV), microvascular blood flow velocity (MFV), and microvascular blood flow (MBF) were determined. Additional rats received GLP-1 or saline for 30 min and muscle insulin clearance/uptake was determined. GLP-1 infusion acutely increased muscle MBV (P < 0.04) within 30 min without altering MFV or femoral blood flow. This effect persisted throughout the 120-min infusion period, leading to a greater than twofold increase in muscle MBF (P < 0.02). These changes were paralleled with increases in plasma NO levels, muscle interstitial oxygen saturation, hind leg glucose extraction, and muscle insulin clearance/uptake. NOS inhibition blocked GLP-1-mediated increases in muscle MBV, glucose disposal, NO production, and muscle insulin clearance/uptake. [HYP] In conclusion, GLP-1 acutely recruits microvasculature and increases basal glucose uptake in muscle via a NO-dependent mechanism.
OUTPUT: | entailment | 20 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. [HYP] In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk.
OUTPUT: | entailment | 21 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (approximately 4.5, approximately 8.3, approximately 13.5, and approximately 23.5 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference x blood flow). With this approach, we found that rates of whole-body and leg glucose uptake were significantly lower in obese than in lean subjects at each glucose plateau. Leg blood flow rates increased from 4.3 +/- 0.4 to 6.5 +/- 0.8 dl/min over the range of glucose in lean subjects (P less than 0.05) but remained unchanged in obese subjects. The apparent maximal capacity (Vmax), based on whole-body and leg glucose uptake, was reduced in obese compared with lean subjects, but the apparent Km was similar in the lean and obese subjects (6-9 mM, NS). To assess the affinity of muscle for glucose extraction independent of changes in muscle plasma flow, we determined the mean half-maximal effective glucose concentration (EG50) and found it was similar in the lean and obese subjects (6.0 +/- 0.3 vs. 6.0 +/- 0.8 mM, NS). [HYP] We conclude that 1) the kinetics of in vivo insulin -mediated glucose uptake in skeletal muscle in human obesity are characterized by reduced Vmax but normal Km; 2) the EG50 for insulin -mediated glucose extraction in skeletal muscle was not 6 mM in both lean and obese subjects, consistent with a Km characteristic of the glucose -transport system; 3) obese subjects were unable to generate increases in blood flow in response to hyperglycemia under hyperinsulinemic conditions, and this contributed significantly to lower rates of leg and whole-body glucose uptake.
OUTPUT: | contradiction | 22 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] The kidney is responsible for a considerable part of the clearance of insulin and C-peptide. Two routes are thought to be involved in the renal extraction of insulin and C-peptide from the circulation: (1) glomerular filtration, and (2) uptake by tubular cells from peritubular capillaries. The aim of the present study was to investigate these processes in non-insulin-dependent diabetes mellitus (NIDDM). For this purpose we measured the renal extraction of inulin, insulin, and C-peptide in 12 NIDDM patients and 16 control subjects during elective heart catheterization. In addition, a 24-h urine sample was obtained from all subjects to assess the fractional clearance of the peptides. The total renal extraction of both insulin and C-peptide exceeded the amount that was extracted by filtration, confirming the supposition that both peptides are cleared by an additional mechanism, most probably peritubular uptake. The peritubular uptake of insulin in the NIDDM group was not significantly different from that in the control subjects, whereas the insulin extraction over the legs was significantly lower in NIDDM than in the controls. The peritubular uptake of C-peptide was significantly lower in NIDDM, while the fractional clearance of C-peptide was significantly higher. The latter indicates that the reabsorption of C-peptide from the luminal side of the tubular cell is impaired in diabetes mellitus. [HYP] We conclude that insulin and C-peptide are cleared by an additional mechanism besides filtration in NIDDM .
OUTPUT: | contradiction | 23 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly attributable to inadequate glucagon secretion. Intra-islet somatostatin (SST) suppression of hypoglycemia-stimulated α-cell glucagon release plays an important role. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by SST receptor type 2 (SSTR2) antagonism of α-cells, which relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes-prone (BBDP) rats mimic insulin-dependent human autoimmune T1D, whereas nondiabetic BBDP rats mimic prediabetes. Diabetic and nondiabetic rats underwent a 3-h infusion of vehicle compared with SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycemia clamped at 3 ± 0.5 mmol/L. Diabetic rats treated with SSTR2a needed little or no glucose infusion compared with untreated rats. We attribute this effect to SSTR2a restoration of the attenuated glucagon response. Direct effects of SSTR2a on α-cells was assessed by resecting the pancreas, which was cut into fine slices and subjected to perifusion to monitor glucagon release. SSTR2a treatment enhanced low-glucose-stimulated glucagon and corticosterone secretion to normal levels in diabetic rats. SSTR2a had similar effects in vivo in nondiabetic rats and promoted glucagon secretion from nondiabetic rat and human pancreas slices. [HYP] We conclude that SST contributes to impaired glucagon responsiveness to hypoglycemia in autoimmune T1D.
OUTPUT: | entailment | 24 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Retinal capillary nonperfusion results in neovascularization of the eye, which is restricted to the retina in less severe cases and progresses to the anterior chamber and the iris angle in the most advanced case, called rubeosis. This angioneogenesis may be induced by the release of retinal growth factors into the vitreous. This study compared levels of the IGF-I and IGF-II, and of the IGF binding protein-2 (IGFBP-2) and IGFBP-3 in vitreous from three groups with different degrees of retinal ischemia, as judged by the extent of neovascularization: a control group without new vessel formation, retinal neovascularization in patients with proliferative diabetic retinopathy, and massive ischemia of various causes resulting in rubeosis. IGF-I and IGFBP-3 were increased 10- and 13-fold in rubeosis (P << 0.01) compared with no ischemia (n = 10), while IGF-II and IGFBP-2 were elevated 2.7- and 4.3-fold (P < 0.01). Within the rubeosis group similar changes were observed independently of the cause of ischemia, which was central vein occlusion, ischemic ophthalmopathy, or intraocular tumor in seven cases and diabetic retinopathy in three samples from two patients. Vitreous from patients with proliferative diabetic retinopathy but without rubeosis (n = 16) contained 2.5- and 2.2-fold elevated levels of IGF-I and of IGFBP-2 (P < 0.05), while IGF-II and IGFBP-3 were increased 1.4- and 1.6-fold, which was not significant. [HYP] We conclude that: (a) IGF-I appears to be a strong stimulus for the local production of ischemia and -II and of IGFBP-2 and -3 in the eye.
OUTPUT: | contradiction | 25 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Exercise training or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors can ameliorate glucose intolerance, insulin resistance of muscle glucose metabolism, and dyslipidemia associated with the obese Zucker rat. The purpose of the present study was to determine the interactions of exercise training and ACE inhibition (trandolapril) on these parameters in the obese Zucker rat. Animals were assigned to a sedentary control, a trandolapril-treated (1 mg. kg-1. day-1 for 6 wk), an exercise-trained (treadmill running for 6 wk), or a combined trandolapril-treated and exercise-trained group. Exercise training, alone or with trandolapril, significantly (P < 0. 05) increased peak O2 consumption by 31-34%. Similar decreases in fasting plasma insulin (34%) and free fatty acids (31%) occurred with exercise training alone or in combination with trandolapril. Compared with control, exercise training or trandolapril alone caused smaller areas under the curve (AUC) for glucose (12-14%) and insulin (28-33%) during an oral glucose tolerance test. The largest decreases in the glucose AUC (40%) and insulin AUC (53%) were observed in the combined group. Similarly, whereas exercise training or trandolapril alone improved maximally activated insulin-stimulated glucose transport in isolated epitrochlearis (26-34%) or soleus (39-41%) muscles, the greatest improvements in insulin action (67 and 107%, respectively) were seen in the combined group and were associated with similarly enhanced muscle GLUT-4 protein and total hexokinase levels. [HYP] In conclusion, these results indicate combined exercise training and ACE inhibition improve oral glucose tolerance and insulin -stimulated muscle glucose transport to a greater extent than does either intervention alone.
OUTPUT: | entailment | 26 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] This study aimed to differentiate the effects of repeated antecedent hypoglycemia, antecedent marked hyperinsulinemia, and antecedent increases in corticosterone on counterregulation to subsequent hypoglycemia in normal rats. Specifically, we examined whether exposure to hyperinsulinemia or elevated corticosterone per se could impair subsequent counterregulation. Four groups of male Sprague-Dawley rats were used: 1) normal controls (N) had 4 days of sham antecedent treatment; 2) an antecedent hypoglycemia group (AH) had 7 episodes of hyperinsulinemic hypoglycemia over 4 days; 3) an antecedent hyperinsulinemia group (AE) had 7 episodes of hyperinsulinemic euglycemia; and 4) an antecedent corticosterone group (AC) had 7 episodes of intravenous corticosterone to simulate the hypoglycemic corticosterone levels in AH rats. On day 5, hyperinsulinemic euglycemic-hypoglycemic clamps were performed. Epinephrine responses to hypoglycemia were impaired (P < 0.05 vs. N) after antecedent hypoglycemia and hyperinsulinemia. This correlated with diminished (P < 0.05 vs. N) absolute glucose production responses in AH rats and diminished incremental glucose production responses in AE rats. Paradoxically, norepinephrine responses were increased (P < 0.05 vs. N) after antecedent hypoglycemia. Glucagon and corticosterone responses were unaffected by antecedent hypoglycemia and hyperinsulinemia. In AC rats, incremental but not absolute glucose production responses were decreased (P < 0.05 vs. N). However, neuroendocrine counterregulation was unaltered. [HYP] We conclude that both antecedent hypoglycemia and hyperinsulinemia impair epinephrine and glucose production responses to subsequent hypoglycemia , suggesting that severe recurrent hyperinsulinemia may contribute to the development of hypoglycemia -associated autonomic failure.
OUTPUT: | entailment | 27 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Glioblastoma (GBM) is the most prevalent malignant tumor in the central nervous system. Aerobic glycolysis, featured with elevated glucose consumption and lactate production, confers selective advantages on GBM by utilizing nutrients to support rapid cell proliferation and tumor growth. Pyruvate kinase 2 (PKM2), the last rate-limiting enzyme of glycolysis, is known to regulate aerobic glycolysis, and considered as a novel cancer therapeutic target. Herein, we aim to describe the cellular functions and mechanisms of a small molecular compound dimethylaminomicheliolide (DMAMCL), which has been used in clinical trials for recurrent GBM in Australia. Our results demonstrate that DMAMCL is effective on the inhibition of GBM cell proliferation and colony formation. MCL, the active metabolic form of DMAMCL, selectively binding to monomeric PKM2 and promoting its tetramerization, was also found to improve the pyruvate kinase activity of PKM2 in GBM cells. In addition, non-targeting metabolomics analysis reveals multiple metabolites involved in glycolysis, including lactate and glucose-6-phosphate, are decreased with DMAMCL treatment. The inhibitory effects of DMAMCL are observed to decrease in GBM cells upon PKM2 depletion, further confirming the importance of PKM2 in DMAMCL sensitivity. [HYP] In conclusion, the activation of PKM2 by DMAMCL results in the rewiring aerobic glycolysis , which consequently suppresses the proliferation of GBM cells.
OUTPUT: | entailment | 28 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, has been reported to possess a variety of health-promoting properties. Emerging evidence indicates that PSPC can suppress postprandial hyperglycemia via inhibition of α-glucosidases. However, the protective effects of PSPC on hepatic insulin resistance and the precise mechanisms underlying these protective effects have never been investigated. In this study, our data showed that PSPC effectively improved the fasting blood glucose level, glucose and insulin tolerance by suppressing reactive oxygen species (ROS) production and by restoring glutathione (GSH) content and antioxidant enzymes' activities. PSPC further prevented the oxidative-stress-mediated endoplasmic reticulum (ER) stress in the livers of high-fat-diet (HFD)-treated mice. Moreover, PSPC dramatically suppressed the c-Jun-N-terminal kinase 1 and I kappa B kinase β activation and nuclear factor-kappa B p65 nuclear translocation caused by oxidative and ER stress in the livers of HFD-treated mice. Ultimately, PSPC notably restored the impairment of the insulin receptor substrate-1/phosphoinositide 3 kinase/protein kinase B (Akt) insulin signaling in the livers of HFD-treated mice. [HYP] In conclusion, our findings indicate that PSPC protected against HFD-induced hepatic insulin resistance via decreasing ER stress level and blocking ER stress -mediated ROS .
OUTPUT: | contradiction | 29 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Previous studies have left unanswered whether human obesity, independent of glucose intolerance, is associated with a "postreceptor" defect in insulin action. We have studied the relationship between the degree of obesity (as estimated by underwater weighing) and the maximal insulin-stimulated glucose disposal rate (M) in vivo in 52 glucose-tolerant Pima Indian males. The relationship was examined independently of differences in age and maximal oxygen uptake (an estimate of "physical fitness"). The maximal insulin-stimulated glucose transport rate (MTR) was also measured in isolated abdominal adipocytes from the same subjects to determine whether differences in M could be explained by differences in glucose transport. The results showed that there was a large variance in M and MTR among these glucose-tolerant subjects. M was better correlated with glucose storage rates than with oxidation rates, as estimated by indirect calorimetry. The most obese subjects had only a 20% lower mean M and 30% lower MTR than the most lean subjects. The lower M in the obese subjects was due to both lower glucose oxidation and storage rates. There was no significant, independent correlation between age or degree of obesity and M or MTR. The maximal oxygen uptake (VO2 max) appeared to independently account for 20% of the variance observed in M. MTR was only weakly correlated with M (r = 0.36, P less than 0.02). [HYP] We concluded that differences in M in these glucose-tolerant subjects must be explained by factor(s) other than maximal oxygen uptake, age, maximal insulin -stimulated glucose transport in vitro, or degree of adiposity per se.
OUTPUT: | entailment | 30 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] The hypothesis that increased intraoperative blood lactate depends both on intraoperative glucose supply and inadequate tissue oxygenation occurring during surgery was tested in anesthetized patients undergoing infrarenal abdominal aortic surgery. Twenty surgical patients received either Ringer's solution or 5% glucose solution for intraoperative volume loading. Arterial blood lactate, arterial glucose, hemodynamic variables, insulin, glucagon, cortisol, epinephrine, and norepinephrine were determined preoperatively and intraoperatively. There were no significant changes in hemodynamic values, glucagon, norepinephrine, and epinephrine compared with control values in both groups. Oxygen consumption decreased only during aortic clamping. Cortisol and lactate increased significantly 10 min after aortic clamping until the end in both groups. Glucose 5% solution infusion resulted in significantly greater blood lactate accumulation and significantly greater blood glucose and insulin levels, whereas there were no changes in the patients receiving Ringer's solution. From control until aortic clamping, lactate and glucose were significantly correlated with each other in both groups; after aortic clamping until the end of the procedure, the correlation remained constant in patients in the Ringer's group, whereas no relationship could be demonstrated in those in the glucose group. [HYP] We conclude that increased intraoperative blood lactate concentrations during abdominal aortic surgery depend on both intraoperative glucose supply and inadequate tissue oxygenation occurring during the procedure.
OUTPUT: | contradiction | 31 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Transforming growth factor-β (TGF-β) is pivotal in the pathogenesis of diabetic nephropathy. Type 1 TGF-β receptor (TGF-βR1) is degraded by Smad7-dependent ubiquitination-proteasomal pathway, which is deubiquitinated by ubiquitin C-terminal hydrolase-L5 (UCHL5). Therefore, we studied the role of UCHL5 in high glucose (27.8mM)-induced TGF-βR1 protein expression in mouse mesangial (MES13) cells. UCHL5 short hairpin RNA (shRNA) was used to knock down UCHL5 while LY294002 and the dominant-negative p85 were used to inhibit phosphatidylinositol-3-kinase (PI3K). We found that high glucose increased phospho-Akt, TGF-βR1 mRNA and protein expression. High glucose also increased UCHL5 protein expression, which was attenuated by LY294002, the dominant-negative p85 and the dominant-negative CREB. High glucose-induced TGF-βR1 protein expression and TGF-βR1 protein deubiquitination were attenuated by UCHL5 shRNA. Additionally, high glucose-induced p21(WAF1), fibronectin protein expression and cell hypertrophy were attenuated by UCHL5 shRNA. However, high glucose-induced TGF-βR1 mRNA, p27(kip1) protein expression and growth inhibition were not affected by UCHL5 shRNA. Finally, glomerular UCHL5 and TGF-βR1 protein expression were increased in streptozotocin-diabetic rats at 8weeks. [HYP] We conclude that PI3K-dependent UCHL5 is required for high glucose -induced TGF-βR1 protein expression in mesangial cells.
OUTPUT: | entailment | 32 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] The macrovascular complications of non-insulin-dependent diabetes mellitus (NIDDM) are related to the features of insulin resistance (IR). High Factor VII:C (FVII:C) levels are associated with increased cardiovascular risk and relate to a base change in the FVII gene detected by Msp I endonuclease, and also to an insertion polymorphism in the promoter region. To examine the association between FVII:C levels, genotype and features of IR, 95 NIDDM patients were studied. Genotype was related to FVII:C levels (M1M1 137%, n = 75; M1M2 and M2M2 114%, n = 20, p < 0.005; AA 136%, n = 71; Aa 119%, n = 21, p < 0.05), which is consistent with previous studies in healthy populations. FVII:C correlated with cholesterol (r = 0.51, p < 0.0005), insulin (r = 0.36, p = 0.002), triglycerides (r = 0.34, p = 0.001), age (r = 0.23, p < 0.005) and body mass index (r = 0.23, p < 0.05). When analysed by Msp I genotype, the stronger predictor of FVII:C levels, these correlations remained, with no difference in regression slopes. In a multiple regression model, genotype, cholesterol, insulin, and gender remained as independent predictors of FVII:C levels. [HYP] In conclusion, FVII:C concentrations are elevated in NIDDM in relation to both FVII genotypes and features of IR.
OUTPUT: | entailment | 33 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] Heat-stressed pigs experience metabolic alterations, including altered insulin profiles, reduced lipid mobilization, and compromised intestinal integrity. This is bioenergetically distinct from thermal neutral pigs on a similar nutritional plane. To delineate differences in substrate preferences between direct and indirect (via reduced feed intake) heat stress effects, skeletal muscle fuel metabolism was assessed. Pigs (35.3 ± 0.8 kg) were randomly assigned to three treatments: thermal neutral fed ad libitum (TN, 21°C, n=8), heat stress fed ad libitum (HS, 35°C, n=8), and TN, pair-fed to HS intake (PF, n=8) for 7 days. Body temperature (TB) and feed intake (FI) were recorded daily. Longissimus dorsi muscle was biopsied for metabolic assays on days -2, 3, and 7 relative to initiation of environmental treatments. Heat stress increased TB and decreased FI (P < 0.05). Heat stress inhibited incomplete fatty acid oxidation (P < 0.05) and did not alter glucose oxidation. Metabolic flexibility decreased in HS pigs compared to TN and PF controls (P < 0.05). Both phosphofructokinase and pyruvate dehydrogenase (PDH) activities increased in PF (P < 0.05), however, TN and HS did not differ. Heat stress inhibited citrate synthase and beta hydroxyacyl-CoA dehydrogenase (βHAD) activities (P < 0.05). Heat stress did not alter PDH phosphorylation or carnitine palmitoyltransferase 1 abundance, but reduced acetyl-CoA carboxylase 1(ACC1) protein abundance (P < 0.05). [HYP] In conclusion, HS decreased skeletal muscle fatty acid oxidation and metabolic flexibility, likely involving βHAD and ACC regulation.
OUTPUT: | entailment | 34 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] This open, prospective therapeutic trial studied the effects of regular moderate androgen supplementation on bone mineral density in eugonadal men with established osteoporosis, and collected data on the safety of androgen therapy used in this setting. 23 men, aged 34-73 years, with vertebral crush fractures and back pain, in whom secondary causes of osteoporosis had been excluded, were treated with fortnightly intramuscular injections of 250 mg testosterone esters (Sustanon 250(R)) for 6 months. Blood pressure was recorded monthly; fasting lipids, glucose, haematocrit, plasma viscosity, and testosterone levels were measured every 3 months. Psychological effects were assessed using the Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), together with questioning on libido changes. Principal outcomes measured were changes in bone mineral density at the hip and spine by dual-energy X-ray absorptiometry (DEXA) over the treatment period. 21 men completed the study period. Mean bone mineral density at the lumbar spine increased from 0.799 g/cm(2) to 0.839 g/cm(2) during treatment (p < 0. 001), a rise of 5% in 6 months. Bone mineral density at the hip did not change. There were significant, favorable changes in diastolic blood pressure (-4.7 mmHg, p < 0.01), serum triglyceride levels (-0.405 mmol/L,p < 0.01), and total cholesterol (-0.27 mmol/L, p < 0.05). Adverse changes included a fall in HDL cholesterol (-0.087 mmol/L, p < 0.05) and a rise in plasma viscosity which was significant at 3 months but not at 6 months. The expected rises in hematocrit (0.434 to 0.456) and FAI (0.504 to 0.887) occurred. [HYP] We conclude that testosterone supplementation significantly increased bone mineral density in this heterogeneous group of men with idiopathic primary osteoporosis , without an overall adverse effect on cardiovascular risk factors.
OUTPUT: | entailment | 35 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Glucokinase (GK) and 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (FBP-2) are each powerful regulators of hepatic carbohydrate metabolism that have been reported to influence each other's expression, activities, and cellular location. Here we present the first physical evidence for saturable and reversible binding of GK to the FBP-2 domain of PFK-2/FBP-2 in a 1:1 stoichiometric complex. We confirmed complex formation and stoichiometry by independent methods including affinity resin pull-down assays and fluorescent resonance energy transfer. All suggest that the binding of GK to PFK-2/FBP-2 is weak. Enzymatic assays of the GK:PFK-2/FBP-2 complex suggest a concomitant increase of the kinase-to-bisphosphatase ratio of bifunctional enzyme and activation of GK upon binding. The kinase-to-bisphosphatase ratio is increased by activation of the PFK-2 activity whereas FBP-2 activity is unchanged. This means that the GK-bound PFK-2/FBP-2 produces more of the biofactor fructose-2,6-bisphosphate, a potent activator of 6-phosphofructo-1-kinase, the committing step to glycolysis. [HYP] Therefore, we conclude that the binding of GK to PFK-2/FBP-2 promotes a coordinated up-regulation of glucose phosphorylation and glycolysis in the liver, i.e.
OUTPUT: | entailment | 36 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] This study was designed to determine the role of CO2 in the cerebral hemodynamic, metabolic, and fluid shift responses in a conscious sheep model of acute mountain sickness (AMS). Ewes were instrumented chronically with left ventricular, aortic, inferior vena cava, sagittal sinus, and epidural catheters and exposed to 96 h of hypoxia in an environmental chamber in two groups: 1) hypocapnic [HH; n = 12; arterial PO2 (PaO2) = 40 Torr, arterial PCO2 (PaCO2) = 27 Torr] and 2) eucapnic (EH; n = 9; PaCO2 = 40 Torr, PaCO2 = 37 Torr). AMS, estimated from food and water intakes and behavior, occurred in 9 of 12 HH and 9 of 9 EH sheep. Intracranial pressure (Picp) and the pressure gradient between Picp and sagittal sinus (Psag) increased in AMS sheep only. Total and regional cerebral blood flows, except in the choroid plexus (Qcp), were elevated significantly (P < 0.05) throughout hypoxia in all sheep; cerebral blood flow was greater in EH sheep (P < 0.05). Qcp decreased in HH (P < 0.05) but remained unchanged in EH sheep. Cerebral O2 and glucose uptakes were not altered in either group. Brain edema, reflected by elevated wet-to-dry tissue weight ratios (P < 0.0001), occurred only in AMS sheep. [HYP] We conclude 1) AMS is associated with cerebral CO2 and normal brain aerobic metabolism, 2) decreased Qcp and increased Picp-Psag gradients during HH likely compensate the increased intracranial volume in AMS, and 3) edema supplementation at constant PaO2 did not reduce AMS, Picp, or brain tissue CO2 .
OUTPUT: | contradiction | 37 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Two biallelic polymorphisms, previously described in the human intercellular adhesion molecule (ICAM)-1 gene at codon 241 (glycine [G] to arginine [R] substitution) and codon 469 (glutamic acid [E] to lysine [K] substitution) have been associated with a number of diseases including myocardial infarction, transplant rejection, and diabetes. However, the functional significance of these polymorphisms has not been determined. ICAM-1 cell surface expression and ICAM-1-mediated leukocyte adhesion were investigated using Cos7 transfected with ICAM-1 polymorphic variants or human umbilical vein endothelial cells (HUVEC) of different ICAM-1 genotypes. There was significantly higher expression of surface ICAM-1 on Cos7 transfected with a plasmid encoding the GE (G241/E469) ICAM-1 variant or untreated HUVEC of GEGE (G241/E469 homozygous genotype). ICAM-1-mediated adhesion of peripheral blood mononuclear cells (PBMC) to GE-Cos7 cells or TNF-treated GEGE HUVEC was significantly increased. However, there was no significant difference in adhesion of PBMC to recombinant ICAM-1 of each polymorphic variant plated onto plastic wells. [HYP] We conclude that the GE genotype of ICAM-1 is associated with greater cell surface expression of ICAM-1 , which in turn leads to greater adhesion of leukocytes.
OUTPUT: | entailment | 38 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. [HYP] In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin -responsive tissues independently from the decrease in energy intake.
OUTPUT: | contradiction | 39 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] The glucoregulatory function of glucagon was investigated in hypo-, eu- and hyperthyroid miniature pigs. Infusion glucagon, (3 ng x kg body weight-1.min-1) transiently increased blood glucose (p less than 0.01) and hepatic glucose production (p less than 0.01) in euthyroidism, but was without effect in hyperthyroidism. Infusing glucagon plus somatostatin (2 ng x kg body weight-1.min-1 and 0.2 microgram x kg body weight-1.min-1) transiently increased blood glucose (delta 3.0 to 4.3 mmol/l) and hepatic glucose production (delta 3.3 to 7.7 mumol x kg body weight-1.min-1) in all thyroid states, the effect was less pronounced in hyperthyroid pigs. By contrast, hypoglucagonaemia (74 to 107 pg/ml) at basal insulin (28 to 35 microU/ml) provoked hypoglycaemia (1.4 to 2.2 mmol/l) and a fall in glucose production (delta 4.7 to 8.3 mumol x kg body weight-1.min-1), which was independent of the thyroid state; the effect was most pronounced in hyperthyroidism (p less than 0.01). Hepatic glycogen content, arterial gluconeogenic precursor concentrations as well as the glycaemic response (delta 0.60 mmol/l) to alanine infusion (23 mumol x kg body weight-1.min-1) were all unaffected by hyperthyroidism. [HYP] We conclude that moderate experimental hyperthyroidism reduces glucagon action due to reduced glycogen mobilisation.
OUTPUT: | entailment | 40 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by -6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and -2% ± 88% (S80) (p = 0.001). [HYP] In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.
OUTPUT: | entailment | 41 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. [HYP] It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.
OUTPUT: | entailment | 42 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] Changes in the maternal nutritional environment during fetal development can influence offspring's metabolic risk in later life. Animal models have demonstrated that offspring of diet-induced obese dams develop metabolic complications, including nonalcoholic fatty liver disease. In this study we investigated the mechanisms in young offspring that lead to the development of nonalcoholic fatty liver disease (NAFLD). Female offspring of C57BL/6J dams fed either a control or obesogenic diet were studied at 8 wk of age. We investigated the roles of oxidative stress and lipid metabolism in contributing to fatty liver in offspring. There were no differences in body weight or adiposity at 8 wk of age; however, offspring of obese dams were hyperinsulinemic. Oxidative damage markers were significantly increased in their livers, with reduced levels of the antioxidant enzyme glutathione peroxidase-1. Mitochondrial complex I and II activities were elevated, while levels of mitochondrial cytochrome c were significantly reduced and glutamate dehydrogenase was significantly increased, suggesting mitochondrial dysfunction. Offspring of obese dams also had significantly greater hepatic lipid content, associated with increased levels of PPARγ and reduced triglyceride lipase. Liver glycogen and protein content were concomitantly reduced in offspring of obese dams. [HYP] In conclusion, offspring of diet-induced obese metabolism have disrupted liver dams and develop NAFLD prior to any differences in body weight or body composition.
OUTPUT: | contradiction | 43 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] The apoptosis of tubular epithelial cells in diabetic nephropathy (DN) is commonly observed in human renal biopsies. Inflammation plays a key role in DN, and pentosan polysulfate (PPS) has been shown to largely attenuate the inflammation of nephropathy in aging diabetic mice. p38 mitogen‑activated protein kinase (p38 MAPK) plays a crucial role in tissue inflammation and cell apoptosis, and it is activated by hyperglycemia. In the present study, high glucose (HG)‑treated human renal proximal tubular epithelial cells (HK‑2) were used to examine the protective effects of PPS against HG‑stimulated apoptosis and inflammation. The results of the study revealed that PPS markedly suppressed the HG‑induced reduction in cell viability. Incubation of HK‑2 cells with HG activated the p38 MAPK pathway and, subsequently, as confirmed by western blot analysis and flow cytometry, increased cell apoptosis, which was blocked by PPS. In addition, PPS treatment significantly inhibited HG‑stimulated p38 MAPK and nuclear factor‑κB activation, and reduced the production of pro‑inflammatory cytokines, such as tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6. [HYP] In conclusion, PPS ameliorates apoptosis ‑mediated renal cell p38 MAPK and inflammation.
OUTPUT: | contradiction | 44 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Diabetic retinopathy (DR) is one of the most common and serious complications of diabetes mellitus (DM). This study aims to investigate the amelioration of chlorogenic acid (CGA) on proliferative DR (PDR) via focusing on inhibiting retinal neoangiogenesis. CGA reduced the increased cell proliferation, migration and tube formation induced by vascular endothelial growth factor (VEGF) in human retinal endothelial cells (HREC) and choroid-retinal endothelial RF/6A cells. CGA abrogated VEGF-induced the phosphorylation of VEGFR2 and its downstream mitogen-activated extracellular regulated kinase (MEK1/2), extracellular regulated protein kinase (ERK1/2) and p38 kinase. CGA reduced high glucose (HG)-induced the activation of microglia BV-2 cells. CGA also reduced HG-induced the increased VEGF expression and hypoxia-inducible factor 1-alpha (HIF-1α) translocation into nucleus in BV2 cells. Retinal immunofluorescence staining with cluster of differentiation 31 (CD31) and retinal histopathological observation both demonstrated that CGA (1, 10mg/kg) decreased the increased retinal vessels in streptozotocin (STZ)-induced hyperglycemic mice. CGA reduced the elevated serum VEGF level and microglia activation in STZ-induced hyperglycemic mice. [HYP] In conclusion, CGA inhibits retinal neoangiogenesis during the process of DR by abrogating HG-induced HIF-1 α-mediated paracrine VEGF expression in microglia cells and inhibiting VEGF-induced angiogenesis in retinal endothelial cells.
OUTPUT: | entailment | 45 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] We have tested the hypothesis that prolonged fetal hypoxemia causes a reduction in glycogenolytic enzyme activities and/or a depletion of fetal glycogen stores. We compared the effects of short (4 h) and prolonged (24 h) periods of reduced maternal uterine blood flow (RUBF) on glycogen content and on the activities of glucose-6-phosphatase (G-6-Pase), glycogen phosphorylase (GPase), and glycogen synthase (GSase) in selected fetal tissues. RUBF was reduced in 10 pregnant sheep at 135 days of gestation (term approximately 146 days) for either 4 h (n = 5) or 24 h (n = 5); 5 other fetuses were used as controls. During RUBF, fetal SaC2 was decreased from 61.6 +/- 3.9 to 22.0 +/- 1.4% at 4 h and to 26.7 +/- 1.2% at 24 h. Hepatic glycogen content was significantly reduced at 4 h of RUBF, but was not reduced further at 24 h. Fetal liver GPase (active and total enzyme activity) and G-6-Pase activities were reduced at 4 h of RUBF but tended to return toward control values at 24 h. Similarly, hepatic GSase activity tended to decrease at 4 h of RUBF, although the reduction was not quite significant (P = 0.08). [HYP] We conclude that RUBF causes a reduction of fetal glycogen stores and a reduction in G-6-Pase and GPase activity at 146 h. Fetal tissue glycogen contents were not reduced further at 24 h, compared with 146 h of RUBF , which indicates that fetal glycogen olysis is reduced during this time, probably because of the inhibition of GPase and G-6-Pase.
OUTPUT: | contradiction | 46 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Previously we demonstrated that the insulin- and amino acid-induced activation of the mammalian target of rapamycin complex 1 (mTORC1) is developmentally regulated in neonatal pigs. Recent studies have indicated that members of the System A transporter (SNAT2), the System N transporter (SNAT3), the System L transporters (LAT1 and LAT2), and the proton-assisted amino acid transporters (PAT1 and PAT2) have crucial roles in the activation of mTORC1 and that the abundance of amino acid transporters is positively correlated with their activation. This study aimed to determine the effect of the post-prandial rise in insulin and amino acids on the abundance or activation of SNAT2, SNAT3, LAT1, LAT2, PAT1, and PAT2 and whether the response is modified by development. Overnight fasted 6- and 26-day-old pigs were infused for 2 h with saline (Control) or with insulin or amino acids to achieve fed levels while amino acids or insulin, respectively, as well as glucose were maintained at fasting levels. The abundance of SNAT2, SNAT3, LAT1, LAT2, PAT1, and PAT2 was higher in muscle of 6- compared with 26-day-old pigs. The abundance of the PAT2-mTOR complex was greater in 6- than in 26-day-old pigs, consistent with the higher activation of mTORC1. Neither insulin nor amino acids altered amino acid transporter or PAT2-mTOR complex abundance. [HYP] In conclusion, the amino acid transporters, SNAT 1/3, LAT 1/1, and PAT1/1, likely have important roles in the enhanced amino acid -induced activation of mTORC1 in skeletal muscle of the neonate.
OUTPUT: | contradiction | 47 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] Qing-Hua Granule (QHG), the modified formulation of a classical Chinese prescription named Gegen Qinlian Decoction, was clinically employed to treat type 2 diabetes mellitus (T2DM) through regulation of glucagon-like peptide-1 (GLP-1). However, the potential mechanism is unknown. We investigate whether QHG induces GLP-1 secretion via activation of bitter taste receptor (TAS2R) pathway in the gastrointestinal tract of db/db mice. The db/db mice were intragastrically (i.g.) administered QHG (low/medium/high dose) once daily for 8 weeks. GLP-1 secretion was evaluated. The bitter receptor signaling pathway, which regulates GLP-1 secretion, including TAS2R5 (a subtype of TAS2R), α-gustducin (Gαgust), 1-phosphatidylinositol-4, 5-bisphosphate phosphodiesterase beta-2 (PLCβ2), transient receptor potential cation channel subfamily M member 5 (TRPM5), was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry (IHC). The biochemical observations of ileum and pancreas tissue were detected histopathologically. Acquity Ultra Performance LCTM - Micromass ZQ 2000 (UPLC-MS) was used for the phytochemical analysis. QHG exhibited significant and dose-dependent effect on GLP-1 secretion in db/db mice, along with significant up-regulation of TAS2R5 mRNA level and activation of TAS2R pathway (p<0.05). In addition, QHG improved the histopathological structure of ileum and pancreatic tissue. Seventeen compounds were identified in QHG. [HYP] In conclusion, QHG induces GLP-1 secretion in db/db mice, most likely through the bitter taste receptor pathway.
OUTPUT: | entailment | 48 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Despite evidence supporting an association between enterovirus (EV) infection and type 1 diabetes, the etiological mechanism(s) for EV-induced beta cell destruction is(are) not well understood. In this study, the effects of Coxsackievirus B (CVB) 1-6 on cell lysis and cytokine/chemokine expression in the insulinoma-1 (INS-1) beta cell line were investigated. Cytolysis was assessed using tissue culture infectious dose 50 (TCID(50)). Quantitative RT-PCR was used to measure viral RNA and mRNA of cytokines interferon (IFN)-α, IFN-β, IFN-γ, tumor necrosis factor (TNF)-α, and chemokine (C-X-C motif) ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-C motif) ligand 5 (CCL5) in infected INS-1 cells. CVB2, 4, 5, and 6 lysed and replicated in INS-1 cells; TCID(50) was lowest for CVB5 and highest for CVB6. IFN-γ, CXCL10, and CCL5 mRNA levels all increased significantly following infection with CVB2, 4, 5, and 6 (P<0.05). CCL2 mRNA increased with CVB2, 5, and 6 (P<0.05), IFN-α mRNA increased with CVB5 infection (P<0.05), while TNF-α mRNA and IFN-β mRNA (P<0.001) increased with CVB2 infection. Dose-dependent effects of infection on cytokine mRNA levels were observed for all (P<0.01) except IFN-γ. Following inoculation of INS-1 cells with CVB1 and 3, viral RNA was not detected and cytokine/chemokine mRNA levels were unchanged. [HYP] In conclusion, CVB2, 4, 5, and 6 induce dose-dependent cytokine and chemokine mRNA production from INS-1 cells suggesting that pro-inflammatory cytokine and chemokine secretion by beta cells is a potential mechanism for EV-induced beta cell damage in type 1 diabetes .
OUTPUT: | entailment | 49 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] Simvastatin was reported to attenuate platelet-derived growth factor (PDGF)-induced vascular smooth muscle proliferation by up-regulation of cyclin dependent kinase (CDK) inhibitor p27, but had no effect on p16, p21, p53 expression. We investigate the mechanisms by which simvastatin inhibits vascular smooth muscle cell (VSMC) growth in high glucose conditions to mimic diabetes. Simvastatin was added to A7r5 cells cultured in high glucose (25 mM) medium, mimicking diabetes. We used an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cell viability; flow cytometric analysis for cell counts distribution in the cell cycle; and Western blot, immunoblotting, and immunoprecipitation analyses to evaluate the effects of simvastatin on CDK activity and cell cycle regulatory proteins. Cell counts were significantly increased in G0/G1 phase and significantly decreased in S and G2/M phases. In our study, low dose of simvastatin had no significant inhibitory effect on VSMC growth in normal glucose condition. However, both low and high doses of simvastatin inhibited VSMC growth significantly in a dose-dependent manner in high glucose status. We also found that simvastatin inhibited phosphorylation of Rb, promoted expression of p53, p16, p21, p27 and decreased CDK2/4 activity. [HYP] In conclusion, cell cycle inhibits VSMC proliferation in high glucose status, mimicking diabetes, inducing a G0/G1 phase simvastatin growth arrest by acting on multiple steps upstream of pRb, including inhibition of CDK2/4 expression and up-regulation of p53, p21, p16, and p27.
OUTPUT: | contradiction | 50 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] Diabetic nephropathy is characterised by an increase in glomerular and tubular fibrosis that compromises kidney function. The transforming growth factor-betas (TGF-betas) have been shown to play a major role in fibrosis and we have shown that TGF-beta2, in particular, increases co-ordinately with fibrogenesis in the diabetic kidney. The aim of this study was to investigate the changes in expression of extracellular matrix molecules in the diabetic kidney, with and without systemic administration of a recombinant human monoclonal antibody to TGF-beta2. Streptozotocin-induced diabetic rats were split into two groups. The first were treated with 5 mg/kg irrelevant control IgG4 (placebo) and the second treated with 5 mg/kg isoform-specific recombinant monoclonal anti-TGF-beta2 IgG4 (termed CAT-152) systemically every second day for 14 days. A further group of six non-diabetic rats was also used as a control. Various biological parameters were measured daily throughout the experimental period, and on termination of the experiment at 14 days Western blotting was performed on kidney cortices for procollagen-I C-propeptide, which is an indicator of the rate of collagen-I synthesis within the kidney. In the placebo-treated diabetic rats, blood glucose, food consumption, urinary albumin excretion (UAE) and kidney weights were all significantly higher than in the non-diabetic group (P<0.05, n=24, by ANOVA). In the anti-TGF-beta2-treated diabetic rats, kidney weights and UAE levels were decreased when compared with those in placebo-treated diabetics. Western blotting for the procollagen-I C-propeptide in kidney cortices showed a significant increase in levels in placebo-treated diabetic rats compared with non-diabetic controls over the 14 day diabetic period, indicating initiation of fibrogenesis. By contrast, in anti-TGF-beta2-treated diabetic rats, levels of the propeptide remained at non-diabetic levels. In summary, a significant suppression of kidney fibrosis was seen in anti-TGF-beta2-treated diabetic rats, compared with placebo-treated diabetic rats. [HYP] We conclude that systemic delivery of CAT-152 , a neutralising anti-TGF-beta2 antibody, during the acute stages of diabetic nephropathy reduces the rate of pathogenic fibrosis in the kidney.
OUTPUT: | entailment | 51 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] High circulating levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are found in patients with hyperinsulinemia. Insulin stimulates release of IL-6 from adipocyte cultures, and it stimulates IL-6 gene expression in insulin-resistant, but not control, rat skeletal muscle. In addition, TNF-alpha may be involved in the pathogenesis of insulin resistance. Therefore, we studied the effect of insulin on IL-6 and TNF-alpha gene expression in human skeletal muscle and adipose tissue. Nine healthy young volunteers participated in the study. They underwent a 6-h hyperinsulinemic euglycemic clamp at a fixed insulin infusion rate, with blood glucose clamped at fasting level. Blood samples drawn at 0, 1, 2, 3, 4, 5, and 6 h were analyzed for IL-6 and TNF-alpha. Muscle and fat biopsies, obtained at 0, 2, 4, and 6 h, were analyzed for IL-6 and TNF-alpha mRNA with real-time PCR. IL-6 mRNA increased 11-, 3-, and 5-fold at 2, 4, and 6 h, respectively, in adipose tissue (ANOVA P = 0.027), whereas there was no significant effect of insulin on skeletal muscles. Plasma IL-6 increased during insulin stimulation. TNF-alpha mRNA increased 2.4-, 1.4-, and 2.2-fold in adipose tissue (ANOVA P = 0.001) and decreased 0.74-, 0.64-, and 0.68-fold in muscle tissue (ANOVA P = 0.04). Plasma levels of TNF-alpha were constant. [HYP] In conclusion, the finding that insulin stimulates IL-6 and TNF-alpha gene expression in adipose tissue only and inhibits the TNF-alpha production in skeletal muscles suggests a differential regulation of muscle- and adipose tissue-derived IL-6 and TNF-alpha.
OUTPUT: | entailment | 52 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Exposure of cardiomyocytes to high glucose concentrations (HG) stimulates reactive oxygen species (ROS) production by NADPH oxidase (NOX2). NOX2 activation is triggered by enhanced glucose transport through a sodium-glucose cotransporter (SGLT) but not by a stimulation of glucose metabolism. The aim of this work was to identify potential therapeutic approaches to counteract this glucotoxicity. In cultured adult rat cardiomyocytes incubated with 21 mM glucose (HG), AMP-activated protein kinase (AMPK) activation by A769662 or phenformin nearly suppressed ROS production. Interestingly, glucagon-like peptide 1 (GLP-1), a new antidiabetic drug, concomitantly induced AMPK activation and prevented the HG-mediated ROS production (maximal effect at 100 nM). α2-AMPK, the major isoform expressed in cardiomyocytes (but not α1-AMPK), was activated in response to GLP-1. Anti-ROS properties of AMPK activators were not related to changes in glucose uptake or glycolysis. Using in situ proximity ligation assay, we demonstrated that AMPK activation prevented the HG-induced p47phox translocation to caveolae, whatever the AMPK activators used. NOX2 activation by either α-methyl-d-glucopyranoside, a glucose analog transported through SGLT, or angiotensin II was also counteracted by GLP-1. The crucial role of AMPK in limiting HG-mediated NOX2 activation was demonstrated by overexpressing a constitutively active form of α2-AMPK using adenoviral infection. This overexpression prevented NOX2 activation in response to HG, whereas GLP-1 lost its protective action in α2-AMPK-deficient mouse cardiomyocytes. Under HG, the GLP-1/AMPK pathway inhibited PKC-β2 phosphorylation, a key element mediating p47phox translocation. [HYP] In conclusion, GLP-47 induces α2-AMPK activation and blocks HG -induced p47phox translocation to the plasma membrane, thereby preventing glucotoxicity.
OUTPUT: | contradiction | 53 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Diabetes mellitus (DM) is a chronic disease in which the body either does not use or produce the glucose metabolising hormone insulin efficiently. Calcification of elastin in the arteries of diabetics is a major predictor of cardiovascular diseases. It has been previously shown that elastin degradation products work synergistically with transforming growth factor-beta 1 (TGF-β1) to induce osteogenesis in vascular smooth muscle cells. In this study, we tested the hypothesis that high concentration of glucose coupled with elastin degradation products and TGF-β1 (a cytokine commonly associated with diabetes) will cause a greater degree of osteogenesis compared to normal vascular cells. Thus, the goal of this study was to analyse the effects of high concentration of glucose, elastin peptides and TGF-β1 on bone-specific markers like alkaline phosphatase (ALP), osteocalcin (OCN) and runt-related transcription factor 2 (RUNX2). We demonstrated using relative gene expression and specific protein assays that elastin degradation products in the presence of high glucose cause the increase in expression of the specific elastin-laminin receptor-1 (ELR-1) and activin receptor-like kinase-5 (ALK-5) present on the surface of the vascular cells, in turn leading to overexpression of typical osteogenic markers like ALP, OCN and RUNX2. Conversely, blocking of ELR-1 and ALK-5 strongly suppressed the expression of the osteogenic proteins. [HYP] In conclusion, our results indicate that glucose plays an important role in amplifying the osteogenesis induced by elastin peptides and TGF-β 1, possibly by activating the ELR-1 and ALK-5 signalling pathways.
OUTPUT: | entailment | 54 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] Mice, deficient for vascular endothelial growth factor VEGF-A in pancreatic islets, have reduced insulin gene expression levels and an impaired glucose tolerance. Here, we investigated whether VEGF-A was required for physiological glucose-stimulated insulin secretion and insulin content. We performed in situ pancreas perfusions and islet perifusions on mice lacking VEGF-A in the pancreatic epithelium in order to study their ability to secrete insulin in response to glucose. We identified insulin secretion defects in the pancreata of VEGF-A deficient mice, including a delayed and blunted response to glucose. Islet perifusion experiments revealed a missing first phase and weaker second phase of insulin secretion, in two of three VEGF-A deficient mice. On average, insulin content in VEGF-A deficient islets was significantly reduced when compared with control islets. [HYP] We conclude that VEGF-A is required in pancreatic islets for normal glucose -stimulated insulin secretion and physiological insulin content.
OUTPUT: | entailment | 55 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] We determined the role of cellular fibronectin (CFN) containing the alternatively spliced extra domain A (FN-EDA) in causing insulin resistance (IR) through toll-like receptor 4 (TLR4). Circulating FN-EDA level was evaluated in mouse and rat IR models. Specific anti-FN-EDA antibody and TLR4 inhibitor were used to study its role in IR in mice. CFN protein was injected to evaluate TLR4 dependent effect of FN-EDA in IR. Furthermore, FN-EDA was estimated in blood plasma and correlated with demographic and clinical characteristics in healthy human participants (n = 38). High-fat diet feeding significantly increased circulating FN-EDA in both mouse (P = 0.03) and rat (P = 0.02) IR models. Antibody against FN-EDA protected mice from IR by increasing glucose disposal rate following glucose (P = 0.02) and insulin (P = 0.01) tolerance tests. CFN protein injection caused IR, however, TLR4 inhibitor protected the mice from CFN induced IR. Multivariate regression analysis predicted an independent positive correlation between circulating FN-EDA and fasting plasma glucose (P = 0.003) in healthy human participants. [HYP] In conclusion, FN-EDA may cause IR through TLR4 by decreasing glucose disposal rate following glucose and insulin load.
OUTPUT: | entailment | 56 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] In summary, this study characterized the biphasic inhibition of fat cell glucose transport by the lipolytic agents caffeine and theophylline. Like the lipolytic drug forskolin, both methylxanthines produced an immediate inhibition of glucose transport that was not seen with 8-phenyltheophylline, a pure adenosine receptor antagonist. The immediate inhibition was therefore not mediated by the adenosine receptor antagonism but seems to be due to a direct interaction with the hexose transporter. This conclusion is supported by the immediate onset of the inhibition and additionally by the interference of theophylline and caffeine with the binding of cytochalasin B, a ligand of the glucose transporter that binds to an intracellular site of the transporter molecule. In addition, a second, delayed inhibitory effect of theophylline and caffeine on glucose transport was observed. This portion shared many aspects of the inhibitory effect of lipolytic hormones. It developed over a period of about 5 min and was antagonized by the simultaneous addition of the antilipolytic hormone PGE2. This component of transport inhibition could be attributed to the antagonistic effect of methylxanthines at the fat cell A1-adenosine receptor since it was also seen with 8-phenyltheophylline. This conclusion is further supported by data showing that the removal of endogenous adenosine with adenosine deaminase resulted in a comparable 25-30% inhibition of insulin-stimulated glucose transport. In addition, the time course of glucose transport inhibition by the subsequent addition of adenosine deaminase is similar to that of the delayed portion of the inhibition seen with theophylline and caffeine. Both treatments produced their maximal inhibition after 5 min. [HYP] In conclusion, the methylxanthines theophylline and glucose transport inhibit caffeine by a combination of two different modes of action.
OUTPUT: | contradiction | 57 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] We examined whether hyperinsulinemia is associated with changes in the amount of L-carnitine and acetyl-L-carnitine in the muscle and whether the source of acetyl-coenzyme A (CoA) (glucose or free fatty acids [FFAs]) influences its further metabolism to acetyl-L-carnitine or through tricarboxylic acid in the skeletal muscle of man in vivo. Twelve healthy men (aged 45 +/- 2 years; body mass index, 25.2 +/- 1.0 kg/m2) were studied using a 4-hour euglycemic-hyperinsulinemic clamp (1.5 mU/kg/min) and indirect calorimetry. Although the mean muscle free L-carnitine and acetyl-L-carnitine concentrations remained unchanged during hyperinsulinemia in the group as a whole, the individual changes in muscle free L-carnitine and acetyl-L-carnitine concentrations were inversely related (r = -.72, P < .02). The basal level of acetyl-L-carnitine was inversely related to the rate of lipid oxidation (r = -.70, P < .02). In a stepwise linear regression analysis, 77% of the variation in the change of acetyl-L-carnitine concentrations was explained by the basal muscle glycogen level (inversely) and nonoxidative glucose disposal rate (directly) during hyperinsulinemia (P < .001); by adding the final FFA concentration (inverse correlation) to the model, 88% of the variation was explained (P < .001). [HYP] In conclusion, hyperinsulinemia reduces the muscle availability of L-carnitine and acetyl-L-carnitine through tricarboxylic acid in vivo.
OUTPUT: | contradiction | 58 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 microM) inhibited glycolysis in hepatocytes incubated with glucose (15-35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with inhibition of glucose-induced dissociation of glucokinase and aldolase. The resorcinol concentration that caused half-maximal inhibition (20-43 microM) increased with increasing glucose concentration (15-35 mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10-200 microM), but it potentiated the stimulation of glycogen synthesis. The inhibition of glycolysis by resorcinol could not be accounted for by diversion of substrate to glycogen. The glucose 6-phosphate content correlated with the free glucokinase activity. Resorcinol counteracted the increase in glucose 6-phosphate and fructose 2,6-bisphosphate caused by elevated glucose concentration or by sorbitol. The suppression of glucose 6-phosphate at high glucose concentration (15-35 mM) could be explained by the low activity of free glucokinase. However, the suppression at 5 mM glucose was due in part to an independent mechanism. The effect of resorcinol on glucokinase translocation was partly counteracted by galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation, and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide. [HYP] It is concluded that resorcinol promotes glycolysis at elevated glucose concentration or when stimulated by sorbitol through increased glucokinase binding.
OUTPUT: | contradiction | 59 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] CTP:phosphocholine cytidylyltransferase (CCT) is a rate-determining enzyme in the de novo synthesis of phosphatidylcholine (PtdCho). Alveolar type II cells synthesize large quantities of disaturated PtdCho, the surface-active agent of pulmonary surfactant, particularly at late gestation when the lung prepares itself for postnatal air breathing. To clarify the role of CCTalpha in lung surfactant maturation, we overexpressed CCTalpha(1-367) using the surfactant protein-C promoter. Lungs of transgenic mice were analyzed at day 18 of gestation (term = 19 days). Overexpression of CCTalpha(1-367) increased the synthesis and content of PtdCho in fetal type II cells isolated from the transgenic mice. Also, PtdCho content of fetal lung fluid was increased. No changes in surfactant protein content were detected. Interestingly, fetal type II cells of transgenic mice contained more glycogen than control cells. Incorporation studies with [U-(14)C]glucose demonstrated that overexpression of CCTalpha(1-367) in fetal type II cells increased glycogen synthesis without affecting glycogen breakdown. To determine which domain contributes to this glycogen phenotype, two additional transgenes were created overexpressing either CCTalpha(1-239) or CCTalpha(239-367). Glycogen synthesis and content were increased in fetal type II cells expressing CCTalpha(239-367) but not CCTalpha(1-239)(.) [HYP] We conclude that overexpression of CCTalpha increases surfactant PtdCho synthesis without affecting surfactant protein levels but that it disrupts glycogen metabolism in differentiating type II cells via its regulatory domain.
OUTPUT: | entailment | 60 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Streptococcus mutans is resistant to bacitracin, which is a peptide antibiotic produced by certain species of Bacillus. The purpose of this study was to clarify the bacitracin resistance mechanism of S. mutans. We cloned and sequenced two S. mutans loci that are involved in bacitracin resistance. The rgp locus, which is located downstream from rmlD, contains six rgp genes (rgpA to rgpF) that are involved in rhamnose-glucose polysaccharide (RGP) synthesis in S. mutans. The inactivation of RGP synthesis in S. mutans resulted in an approximately fivefold-higher sensitivity to bacitracin relative to that observed for the wild-type strain Xc. The second bacitracin resistance locus comprised four mbr genes (mbrA, mbrB, mbrC, and mbrD) and was located immediately downstream from gtfC, which encodes the water-insoluble glucan-synthesizing enzyme. Although the bacitracin sensitivities of mutants that had defects in flanking genes were similar to that of the parental strain Xc, mutants that were defective in mbrA, mbrB, mbrC, or mbrD were about 100 to 120 times more sensitive to bacitracin than strain Xc. In addition, a mutant that was defective in all of the mbrABCD genes and rgpA was more sensitive to bacitracin than either the RGP or Mbr mutants. [HYP] We conclude that RGP synthesis is related to mbr genes resistance in S. mutans and that the bacitracin modulate resistance to mbr genes via an unknown mechanism that is independent of RGP synthesis.
OUTPUT: | contradiction | 61 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-α dependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF ����B (p65) in the livers of KO mice. [HYP] We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation , and damage through mechanisms that do not depend on PPAR-α.
OUTPUT: | entailment | 62 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Catecholamine release is known to be regulated by feedforward and feedback mechanisms. Norepinephrine (NE) and epinephrine (Epi) concentrations rise in response to stresses, such as exercise, that challenge blood glucose homeostasis. The purpose of this study was to assess the hypothesis that the lactate anion is involved in feedback control of catecholamine concentration. Six healthy active men (26 +/- 2 yr, 82 +/- 2 kg, 50.7 +/- 2.1 ml.kg(-1).min(-1)) were studied on five occasions after an overnight fast. Plasma concentrations of NE and Epi were determined during 90 min of rest and 90 min of exercise at 55% of peak O2 consumption (VO2 peak) two times with exogenous lactate infusion (lactate clamp, LC) and two times without LC (CON). The blood lactate profile ( approximately 4 mM) of a preliminary trial at 65% VO2 peak (65%) was matched during the subsequent LC trials. In resting men, plasma NE concentration was not different between trials, but during exercise all conditions were different with 65% > CON > LC (65%: 2,115 +/- 166 pg/ml, CON: 1,573 +/- 153 pg/ml, LC: 930 +/- 174 pg/ml, P < 0.05). Plasma Epi concentrations at rest were different between conditions, with LC less than 65% and CON (65%: 68 +/- 9 pg/ml, CON: 59 +/- 7 pg/ml, LC: 38 +/- 10 pg/ml, P < 0.05). During exercise, Epi concentration showed the same trend (65%: 262 +/- 37 pg/ml, CON: 190 +/- 34 pg/ml, LC: 113.2 +/- 23 pg/ml, P < 0.05). [HYP] In conclusion, lactate attenuates the catecholamine response during moderate-intensity exercise, likely by feedback inhibition.
OUTPUT: | entailment | 63 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] The effects of a daily porcine somatotropin injection on protein synthesis rate in muscle (longissimus), liver and intestine, as influenced by dietary protein, were investigated in 17 pigs. The measurements were made at wk 3 of treatment following 1 wk for adaptation to the diet and 1 wk for determination of nitrogen balance. The fractional rates of protein synthesis in the muscle, liver and intestine were measured using a flooding dose of L-[1-13C]valine. Positive responses of weight gain and nitrogen balance were observed, primarily at higher dietary protein intake, after porcine somatotropin treatment. As expected, porcine somatotropin-treated pigs had a higher proportion of muscle and less fat. Fractional protein synthesis rate was 16% higher in the liver of porcine somatotropin-treated pigs (P < 0.05). In the longissimus muscle fractional protein synthesis rate increased with porcine somatotropin dose from 3.2 to 3.7%/d and from 4.1 to 5.1%/d at low and high protein intake, respectively (P < 0.05). The effect of dietary protein on fractional protein synthesis rate in longissimus was significant, but there was no porcine somatotropin x protein interaction. Ribonucleic acid concentration followed the same pattern as fractional protein synthesis rate in liver and longissimus. In the duodenal tissue, porcine somatotropin treatment depressed fractional protein synthesis rate (P < 0.05) without an effect of dietary protein and RNA concentration did not change. In porcine somatotropin compared with placebo-treated pigs, plasma glucose, insulin and insulin-like growth factor-I concentrations were elevated whereas plasma thyroxine was depressed and plasma triiodothyronine remained constant. There was no clear effect of dietary protein on plasma hormones. [HYP] We concluded that, in pigs fed an adequate level of protein, porcine somatotropin stimulates protein synthesis in the liver and the muscle, primarily through increased ribosomal capacity.
OUTPUT: | entailment | 64 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] To examine the association between von Willebrand Factor (vWF) concentrations and features of the insulin resistance syndrome, 208 patients with Type 2 (non-insulin-dependent) diabetes (NIDDM) and 80 healthy controls were studied. A restriction fragment length polymorphism in exon 12 of the vWF gene, detected by Aat II endonuclease, was also examined. vWF concentrations were elevated in the patient group (patients 1.28 IU ml-1 vs controls 1.12 IU ml-1, p = 0.003). Genotype frequencies were in Hardy-Weinberg equilibrium and genotype did not relate to vWF levels: means (95% CI) were AA 1.29 (1.29-1.44) IU ml-1 n = 3; AG 1.28 (1.22-1.26) IU ml-1 n = 48; GG 1.29 (1.25-1.39) IU ml-1 n = 155. vWF correlated with age (r = 0.23 p < 0.0005), duration of diabetes (r = 0.23, p < 0.001), and fibrinogen (r = 0.22, p = 0.002) in the patient group, but was unrelated to blood lipids, HbA1C, body mass index, glucose, hypertension, and smoking. In a linear regression model, age and insulin remained as independent predictors of vWF levels, explaining 16% of inter-individual variance in the patient group. [HYP] In conclusion, these findings show vWF concentrations are elevated in NIDDM and are weakly related to features of the insulin resistance syndrome.
OUTPUT: | entailment | 65 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] Diazepam-binding inhibitor (DBI) has been localized immunohistochemically in many organs. In porcine and rat pancreas, DBI is present in non-B-cells of the pancreatic islets. Porcine peptide also has been shown to suppress insulin secretion from rat pancreas in vitro. Recently, acyl-CoA-binding protein (ACBP) was isolated from rat liver and shown to be identical structurally to DBI isolated from rat brain. Using this rat DBI/ACBP, we have studied its effects on glucose-stimulated insulin secretion in the rat, both in vivo and in isolated pancreatic islets. Infusion iv of rDBI/ACBP (25 pmol/min) during glucose stimulation induced a moderate and transient reduction of plasma insulin levels. Moreover, rDBI/ACBP suppressed insulin release from batch-incubated isolated islets, stimulated by 16.7 mmol/l glucose, by 24% at 10 nmol/l (p < 0.05) and by 40% at 100 nmol/l (p < 0.01). The peptide (100 nmol/l) also inhibited the insulin response to glucose (16.7 mmol/l) from perifused rat islets by 31% (p < 0.05), mainly by affecting the acute-phase response. Finally, incubation of isolated islets in the presence of rDBI/ACBP antiserum (diluted 1:100 and 1:300) augmented the insulin response to 16.7 mmol/l glucose (p < 0.05 or even less). [HYP] We conclude that rDBI/ ACBP , administered iv or added to the incubation media, suppresses insulin secretion in the rat but that the effect is moderate despite the high concentration used.
OUTPUT: | entailment | 66 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Glioblastoma (GBM) is the most common and malignant type of primary brain tumor and associated with a devastating prognosis. Signal transducer and activator of transcription number 3 (STAT3) is an important pathogenic factor in GBM and can be specifically inhibited with Stattic. Metformin inhibits GBM cell proliferation and migration. Evidence from other tumor models suggests that metformin inhibits STAT3, but there is no specific data on brain tumor initiating cells (BTICs).We explored proliferation and migration of 7 BTICs and their differentiated counterparts (TCs) after treatment with Stattic, metformin or the combination thereof. Invasion was measured in situ on organotypic brain slice cultures. Protein expression of phosphorylated and total STAT3, as well as AMPK and mTOR signaling were explored using Western blot. To determine functional relevance of STAT3 inhibition by Stattic and metformin, we performed a stable knock-in of STAT3 in selected BTICs.Inhibition of STAT3 with Stattic reduced proliferation in all BTICs, but only in 4 out of 7 TCs. Migration and invasion were equally inhibited in BTICs and TCs. Treatment with metformin reduced STAT3-phosphorylation in all investigated BTICs and TCs. Combined treatment with Stattic and metformin led to significant additive effects on BTIC proliferation, but not migration or invasion. No additive effects on TCs could be detected. [HYP] In conclusion, metformin specifically inhibits STAT3 in BTICs, but not in TCs.
OUTPUT: | contradiction | 67 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Increased food intake (FI) during television viewing has been reported in children, but it is unknown if this occurs following pre-meal video game playing (VGP). The objective was to determine the effect of pre-meal VGP for 30 min on subjective appetite and emotions, and FI in normal weight (NW) boys after a glucose or control preload. On four test mornings, NW boys (n = 19) received equally sweetened preloads of a non-caloric sucralose control or 50 g glucose in 250 mL of water, with or without VGP for 30 min. Food intake from an ad libitum pizza meal was measured immediately after. Subjective appetite was measured at 0, 15, 30, and 60 min. Subjective emotions were determined by visual analog scale at baseline and immediately before lunch. Both VGP (p = 0.023) and glucose (p <0.001) suppressed FI. Pre-meal VGP compared with no-VGP, and glucose compared with the non-caloric control, decreased FI by 59 and 170 kcal, respectively. Subjective average appetite increased to 30 min (p = 0.003), but was lower after glucose (p = 0.01) in both the VGP and no-VGP conditions compared with the control. Frustration and aggression scores increased after VGP (p <0.05), but did not correlate with FI. However, baseline and pre-meal happiness and excitement scores were inversely associated with FI. [HYP] In conclusion, both pre-meal VGP and the glucose preload suppressed FI , supporting the roles of both physiologic and environmental factors in the regulation of short-term FI in 9- to 14-year-old NW boys.
OUTPUT: | entailment | 68 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Inadvertent leakage of noncytotoxic agents causes severe tissue injury. In this study, we macroscopically and histopathologically evaluated the extent of skin injury caused by extravasation of hyperosmolar or vasopressor agents in rats. Rats were intradermally administered saline (100 µL), the hyperosmolar agents mannitol (5-20 mg/100 µL) and glucose (5-50 mg/100 µL), or the vasopressors dopamine (2 mg/100 µL), adrenaline (0.1 mg/100 µL), and noradrenaline (0.1 mg/100 µL). Lesion size (erythema, induration, ulceration, and necrosis) was monitored after agent injection. Skin tissue biopsies were evaluated at 24 h after agent injection. Mannitol and glucose induced severe lesions in a concentration (and osmolarity)-dependent manner. Mannitol and glucose at 10-20% (w/v) induced inflammation, and lesions healed within 3-6 d. In contrast, ≥25% (w/v) glucose elicited severe skin lesions with ulceration and necrosis within 24 h, which healed gradually 16-22 d after injection. The severity of extravasation injury caused by vasopressors varied. Adrenaline and noradrenaline induced severe injury with ulceration and necrosis, which healed over 23.3 and 18.3 d, respectively. [HYP] In contrast, dopamine induced erythema and induration, and damage duration was only 5.7 d. In conclusion, mannitol and glucose at osmolarities of 549-1098 and 833-0.1 mOsm/L, respectively, can be classified as "irritants," while ≥1388 mOsm/L glucose can be classified as a "vesicant."
OUTPUT: | contradiction | 69 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Escherichia coli possesses a soluble flavohemoglobin, with an unknown function, encoded by the hmp gene. A monolysogen containing an hmp-lacZ operon fusion was constructed to determine how the hmp promoter is regulated in response to heme ligands (O2, NO) or the presence of anaerobically utilized electron acceptors (nitrate, nitrite). Expression of the phi (hmp-lacZ)1 fusion was similar during aerobic growth in minimal medium containing glucose, glycerol, maltose, or sorbitol as a carbon source. Mutations in cya (encoding adenylate cyclase) or changes in medium pH between 5 and 9 were without effect on aerobic expression. Levels of aerobic and anaerobic expression in glucose-containing minimal media were similar; both were unaffected by an arcA mutation. Anaerobic, but not aerobic, expression of phi (hmp-lacZ)1 was stimulated three- to four-fold by an fnr mutation; an apparent Fnr-binding site is present in the hmp promoter. Iron depletion of rich broth medium by the chelator 2'2'-dipyridyl (0.1 mM) enhanced hmp expression 40-fold under anaerobic conditions, tentatively attributed to effects on Fnr. At a higher chelator concentration (0.4 mM), hmp expression was also stimulated aerobically. Anaerobic expression was stimulated 6-fold by the presence of nitrate and 25-fold by the presence of nitrite. Induction by nitrate or nitrite was unaffected by narL and/or narP mutations, demonstrating regulation of hmp by these ions via mechanisms alternative to those implicated in the regulation of other respiratory genes. Nitric oxide (10 to 20 microM) stimulated aerobic phi (hmp-lacZ)1 activity by up to 19-fold; soxS and soxR mutations only slightly reduced the NO effect. [HYP] We conclude that hmp expression is negatively regulated by Fnr under anaerobic conditions and that additional regulatory mechanisms are involved in the responses to oxygen, nitrogen compounds, and iron availability.
OUTPUT: | entailment | 70 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Diabetic cardiomyopathy (DCM) has become a major cause of diabetes-related morbidity and mortality. Increasing evidences have proved that hydrogen sulfide (H2S) fulfills a positive role in regulating diabetic myocardial injury. The present study was designed to determine whether GYY4137, a novel H2S-releasing molecule, protected H9c2 cells against high glucose (HG)-induced cytotoxicity by activation of the AMPK/mTOR signal pathway. H9c2 cells were incubated in normal glucose (5.5 mM), 22, 33, and 44 mM glucose for 24 h to mimic the hyperglycemia in DCM in vitro. Then we added 50, 100, and 200 μM GYY4137, and measured the cell viability, lactate dehydrogenase (LDH) enzyme activity, and mitochondrial membrane potential (MMP). 0.5 mM 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) and 1 mM adenine 9-β-D-arabinofuranoside (Ara-A, an AMPK inhibitor) were used to identity whether the AMPK/mTOR signal pathway was involved in GYY4137-mediated cardioprotection. We demonstrated that HG decreased cell viability and increased LDH enzyme activity in a concentration-dependent manner. 33 mM HG treatment for 24 h was chosen as our model group for further study. Both 100 and 200 μM GYY4137 treatments significantly attenuated HG-induced cell viability decrement, LDH enzyme activity increase, and MMP collapse. AICAR had similar effects to GYY4137 treatment while Ara-A attenuated GYY4137-mediated cardioprotection. Importantly, both GYY4137 and AICAR increased AMPK phosphorylation and decreased mTOR phosphorylation compared with the HG model group while Ara-A attenuated GYY4137-mediated AMPK phosphorylation increase and mTOR phosphorylation decrement. [HYP] In conclusion, GYY4137 attenuated HG -induced cytotoxicity in H9c2 cells by activating the AMPK /mTOR signal pathway.
OUTPUT: | contradiction | 71 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] The effects of dietary supplementation of dihydroxyacetone and pyruvate (DHAP) on metabolic responses and endurance capacity during leg exercise were determined in eight untrained males (20-30 yr). During the 7 days before exercise, a high-carbohydrate diet was consumed (70% carbohydrate, 18% protein, 12% fat; 35 kcal/kg body weight). One hundred grams of either Polycose (placebo) or dihydroxyacetone and pyruvate (treatment, 3:1) were substituted for a portion of carbohydrate. Dietary conditions were randomized, and subjects consumed each diet separated by 7-14 days. After each diet, cycle ergometer exercise (70% of peak oxygen consumption) was performed to exhaustion. Biopsy of the vastus lateralis muscle was obtained before and after exercise. Blood samples were drawn through radial artery and femoral vein catheters at rest, after 30 min of exercise, and at exercise termination. Leg endurance was 66 +/- 4 and 79 +/- 2 min after placebo and DHAP, respectively (P less than 0.01). Muscle glycogen at rest and exhaustion did not differ between diets. Whole leg arteriovenous glucose difference was greater (P less than 0.05) for DHAP than for placebo at rest (0.36 +/- 0.05 vs. 0.19 +/- 0.07 mM) and after 30 min of exercise (1.06 +/- 0.14 vs. 0.65 +/- 0.10 mM) but did not differ at exhaustion. Plasma free fatty acids, glycerol, and beta-hydroxybutyrate were similar during rest and exercise for both diets. Estimated total glucose oxidation during exercise was 165 +/- 17 and 203 +/- 15 g after placebo and DHAP, respectively (P less than 0.05). [HYP] It is concluded that feeding of DHAP for 7 days in conjunction with a high carbohydrate diet enhances leg exercise endurance capacity by increasing glucose extraction by muscle.
OUTPUT: | entailment | 72 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] Pomegranate peel is an agro-industrial residue obtained after fruit processing with high total polyphenol (TP) content, making it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favouring mitochondrial biogenesis and function have also been described. However, once phenolic compounds are extracted, their stability can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation into functional foods. Nevertheless, studies on the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. This study aims to evaluate the effect of MPPE on brown adipose tissue (BAT) mitochondrial structure and function and metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a wall material and physically-chemically characterised. Eight-week-old male C57BL/6J mice (n 40) were randomly distributed into five groups: control diet (CD), HFD, HFD + IN, HFD + PPE (50 mg/kg per d TP) and HFD + MPPE (50 mg/kg per d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. Blood and adipose tissue samples were obtained. MPPE supplementation prevented HFD-induced body weight gain (P < 0·001), fasting glycaemia (P = 0·007) and total cholesterol rise (P = 0·001). MPPE resulted in higher BAT mitochondrial complex IV activity (P = 0·03) and prevented HFD-induced mitochondrial cristae alteration (P = 0·02). [HYP] In conclusion, body weight prevented HFD-induced excessive MPPE gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae structure in BAT in mice fed with a HFD.
OUTPUT: | contradiction | 73 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] The effect of dietary n-3 or n-6 polyunsaturated fatty acids on the development of autoimmune insulitis was analysed in diabetes-prone BB rats. Litter-matched groups of rats received a standard open formula NIH-07 (National Institutes of Health, NIH) diet enriched with 10% fish oil, 10% flaxseed oil or with 10% palm oil plus 2% cholesterol during the period of insulitis onset (50-70 days of age). Analysis of cytokine gene expression in pancreatic RNA revealed an increase of IFN-gamma and a decrease of IL-10 mRNA with onset of insulitis. When compared to unsupplemented NIH, none of the three fat-enriched diets depressed the rise of IFN-gamma gene expression or the influx of leukocytes into islets. However, all of the fat-enriched diets led to significantly higher IL-10 mRNA levels. Although a specific anti-inflammatory effect of fish oil was not seen in the pancreas, a clear shift of the Th1/Th2 cytokine mRNA ratio towards Th2 was seen in the gut-associated immune system. [HYP] We conclude that diets high in fat support IL-2 without suppressing IFN-gamma gene expression in islet inflammation.
OUTPUT: | contradiction | 74 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] In a previous report we found extreme hyperinsulinemia associated with high testosterone levels in patients with polycystic ovarian syndrome (PCO) and normal insulin levels in a small group of patients with elevated dehydroepiandrosterone (DHEA). From these observations, we hypothesized that DHEA and testosterone may have opposing actions on insulin sensitivity. To test this hypothesis, we studied insulin sensitivity in vivo and in vitro in a) obese PCO women with elevated testosterone, b) obese patients with adult-onset adrenal hyperplasia (AH) and high levels of DHEA, c) weight-matched obese controls, and d) lean controls. Insulin sensitivity was determined by insulin responses to a standard OGTT, hypoglycemic responses to an IV insulin tolerance test (ITT), red blood cell (RBC) insulin binding and receptor kinase activity, and phytohemagglutinin (PHA)-activated T-lymphocyte (T-cell) insulin binding and PDH insulin sensitivity. In PCO patients, we found that basal and glucose-challenged insulin levels were significantly greater than, and hypoglycemic responses to IV insulin, significantly lower than, weight-matched control values. However, AH patients had insulin values significantly below, and hypoglycemic responses significantly above, those of the weight-matched controls. Their values were, in fact, comparable to those observed for the lean control subjects. Similar findings were observed with insulin binding and PDH insulin sensitivity. Insulin sensitivity in all study subjects was found to be negatively correlated to testosterone and positively correlated to DHEA and, more significantly, to the ratio of DHEA/testosterone. These data would suggest that, in females, DHEA and T may have opposing actions on insulin sensitivity. [HYP] We conclude that in females insulin sensitivity in vivo and in vitro is modulated, at least in part, by the ratios of DHEA to testosterone.
OUTPUT: | entailment | 75 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] We previously reported that circulating levels of pigment epithelium-derived factor (PEDF), a newly identified adipokine, are increased in patients with type 2 diabetes, correlating with body mass index. However, the role of PEDF in adipogenesis remains elusive. In the present study, we have investigated the effects and mechanisms of PEDF on adipocyte differentiation in 3T3-L1 preadipocytes. Differentiation of 3T3-L1 preadipocytes was induced in the presence or absence of human recombinant PEDF protein. The effects of PEDF on adipogenic gene expression, mitotic clonal expansion (MCE), and MAPK activation were investigated. Physiological concentrations of human PEDF protein inhibited adipocyte differentiation, evidenced by decreased lipid accumulation, downregulation of adipocyte markers, and inhibition of master adipogenic transcription factors such as C/EBP-alpha and PPARgamma. The antiadipogenic effects of PEDF were observed only when PEDF was added to the cells on day 0, but not on day 3 during differentiation, suggesting that PEDF targets some early adipogenic events. Similarly, overexpression of PEDF by adenovirus attenuated adipocyte differentiation. Further studies revealed that PEDF, or U-0126, a specific MAPK/ERK inhibitor, sequentially inhibited the early activation of ERK and MCE. Moreover, PEDF attenuated expression and the phosphorylation of C/EBP-beta at Thr(188), an essential step for transcriptional activation of C/EBP-beta. In addition, PEDF expression was decreased significantly in the first 24 h during adipocyte differentiation, suggesting that downregulation of PEDF may be essential for the initiation of MCE and adipogenesis. [HYP] We conclude that PEDF promotes adipogenesis in 3T3-L1 preadipocytes partially because of inhibition of the MAPK/ERK signaling pathway and MCE.
OUTPUT: | contradiction | 76 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] We studied the influence of glucose/glucose 6-phosphate cycling on glycogen deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626, specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase respectively. The effect of amino acids and oleate was also examined. The following observations were made: (1) with glucose alone, net glycogen production was low. Inhibition of glucose-6-phosphate translocase increased intracellular glucose 6-phosphate (3-fold), glycogen accumulation (5-fold) without change in active (dephosphorylated) glycogen synthase (GSa) activity, and lactate production (4-fold). With both glucose 6-phosphate translocase and glycogen phosphorylase inhibited, glycogen deposition increased 8-fold and approached reported in vivo rates of glycogen deposition during the fasted-->fed transition. Addition of a physiological mixture of amino acids in the presence of glucose increased glycogen accumulation (4-fold) through activation of GS and inhibition of glucose-6-phosphatase flux. Addition of oleate with glucose present decreased glycolytic flux and increased the flux through glucose 6-phosphatase with no change in glycogen deposition. With glucose 6-phosphate translocase inhibited by S4048, oleate increased intracellular glucose 6-phosphate (3-fold) and net glycogen production (1.5-fold), without a major change in GSa activity. [HYP] We conclude that intracellular glucose 6-phosphate drives net glycogen deposition from glucose in fasted-rat hepatocytes.
OUTPUT: | contradiction | 77 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Recently, we reported that C-reactive protein (CRP) elicits inflammatory and procoagulant responses in humans. In addition, CRP has been associated with the development of type 2 diabetes mellitus. To further explore interactions between CRP and glucose handling, we evaluated the effects of CRP infusion on glucose metabolism in humans. Seven healthy white male volunteers (age, 39.3 +/- 16.9 years) received a single bolus infusion of 1.25 mg/kg purified recombinant human (rh) CRP or CRP-free diluent in a crossover design. C-reactive protein infusion induced an inflammatory response, which was followed by increased plasma concentrations of norepinephrine (3 hours) and cortisol (4 hours). Concomitantly, plasma concentrations of insulin and C-peptide decreased transiently. These metabolic changes increased plasma glucose concentrations from 8 hours after CRP infusion, which was preceded by an increased rate of glucose appearance that was a direct consequence of increased gluconeogenesis. [HYP] In conclusion, CRP infusion induces an inflammatory response followed by increased norepinephrine and cortisol levels, which results in increased gluconeogenesis.
OUTPUT: | entailment | 78 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] The serum pancreatic polypeptide response to intravenous Boots secretin (1.5 U/kg), glucose tolerance, and insulin responses have been studied in 25 patients with chronic alcohol induced pancreatitis of varying severity, and these results compared with a secretin-pancreozymin test, and the structural damage noted on pancreatography. For the pancreatic polypeptide response 16 healthy subjects acted as controls. There was a marked reduction in pancreatic polypeptide response in patients with advanced structural changes of chronic alcohol induced pancreatitis compared with patients with minimal/moderate changes (p less than 0.01) and with healthy controls (p less than 0.05) although there was no difference between the latter two groups. Similarly, while the ratio of peak to mean basal pancreatic polypeptide concentration was also significantly reduced in patients with advanced changes compared with healthy controls (p less than 0.05) there was a marked degree of overlap in patients with lesser degrees of structural damage and control subjects. For all patients with chronic alcohol induced pancreatitis, however, there was a significant correlation between the pancreatic polypeptide response and each parameter of the standard secretin-pancreozymin test and with glucose tolerance and the integrated insulin response. [HYP] We conclude therefore that while the secretin stimulated pancreatic polypeptide response correlates significantly with accepted tests of pancreatic structure and function, there is a significant degree of overlap in the response obtained in patients who have minimal/moderate damage and healthy controls making the test insufficiently sensitive for routine diagnostic use.
OUTPUT: | entailment | 79 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] The in vitro effects of storage of platelets prepared from 4 or 6 pooled buffy coat (BC) units and stored in a platelet storage medium consisting of 30-40% of CPD plasma or alternatively half-strength citrate CPD (0.5 CPD) plasma and 60-70% of different alternative platelet additive solutions (PASs) were evaluated. Measurements of mean platelet volume, pH, pO2, pCO2, bicarbonate, glucose, lactate, ATP, total adenine nucleotide content, extracellular lactate dehydrogenase or adenylate kinase activity, as markers for disintegration of platelets, and extracellular beta-thromboglobulin, as a marker for activation of platelets, were included in the in vitro studies. Previous studies indicated that a reduction of the citrate concentration from the standard 21 to 8 mmol/l is associated with a significant reduction of the consumption of glucose and production of lactate. Alternatively, similar effects can be obtained by the addition of acetate. In a preliminary paired study, the effects of different concentrations of acetate were tested. In an additional paired study, the effects of CPD plasma in combination with either saline or a PAS containing NaCl (115.5 mmol/l), citrate (10 mmol/l), and acetate (30 mmol/l), pH 7.2 (PAS-2) were evaluated. 0.5CPD plasma in combination with either PAS-2 or a nonacetate PAS (PAS-1) were also tested. The storage of platelets in 0.5CPD plasma was used as a reference. [HYP] The conclusions are: (1) A minimum acetate concentration of 30 mmol/l is not needed to counteract the effects of citrate on the production of lactate .
OUTPUT: | contradiction | 80 |
bionli | train | nli | Given a premise and a hypothesis, determine their relationship: entailment, contradiction, or neutral. | [PRE] Ingested fat releases CCK, causes gastric relaxation, delays gastric emptying, and limits meal size; however, the mechanistic link among these actions has not been established. Fatty acid release of CCK is chain-length sensitive; dodecanoic acid (C12) induces greater CCK release than decanoic acid (C10). The effect of C12 or C10 on tolerance to subsequent intragastric infusion of liquid was determined in healthy subjects, with and without the CCK(1) receptor antagonist dexloxiglumide. Gastric wall relaxation after either fatty acid was assessed by graded volume distension and by barostat; gastric emptying was measured by gastric aspiration and by a [(13)C]octanoic acid breath technique. C12 released more CCK (mean plasma CCK after vehicle, 4.7 +/- 0.8 pM; C10, 4.8 +/- 0.3 pM; C12, 8 +/- 1.2 pM; P < 0.05 C12 vs. C10 or vehicle) and reduced the volume of water (and of 5 and 25% glucose solutions) delivered at maximum tolerance compared with C10 or vehicle (volume of water tolerated after vehicle, 1,535 +/- 164 ml; C10, 1,335 +/- 160 ml; C12, 842 +/- 103 ml; P < 0.05 C12 vs. C10 or vehicle); this effect was abolished by dexloxiglumide. Intragastric volumes were always similar at the limit of tolerance, and, whereas gastric relaxation occurred to similar degrees after the fatty acids, its duration was longer after C12, which also induced a longer delay in half-gastric emptying [t(1/2)(min) after vehicle, 53 +/- 2; C10, 67 +/- 3; C12, 88 +/- 7; P < 0.05 C12 vs. C10 or vehicle]. [HYP] We conclude that fatty acid release of CCK induces gastric relaxation, delays gastric emptying , and limits meal size.
OUTPUT: | contradiction | 81 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] In most patients with acromegaly basal serum GH concentrations are elevated and remain above 5 micrograms/L after oral glucose administration. In some patients, however, serum insulin-like growth factor I (IGF-I) concentrations are elevated with only minimal elevations of serum GH. We studied the serum GH and IGF-I of two such patients to determine whether these peptide hormones are normal in this clinical situation. The serum GH of these patients was found to bind normally to receptors of the IM-9 lymphocyte. The elution pattern of IGF-I extracted from the patients' serum was similar to that of (Thr59) human IGF-I after passage through a Bio-Rad P-60 column in 0.5 M acetic acid. The IGF-I was further characterized by isoelectric focusing and C18 reverse phase high pressure liquid chromatography (HPLC). The isoelectric points of the IGF-I components were similar to those of IGF-I in normal serum. The IGF-I in one patient had two components by HPLC, while that of the other patient had only one major component. The IGF-I components isolated by HPLC were normally active in stimulating [3H] alpha-aminoisobutyric acid uptake by normal human fibroblasts. The elevated serum IGF-I concentrations of these two patients were GH dependent. Transsphenoidal adenomectomy in one patient resulted in a decline in serum IGF-I to a high normal concentration. Lowering the serum GH to subnormal concentrations by the administration of the somatostatin analog SMS 201-995 (Sandoz) restored normal IGF-I concentrations in the second patient. [HYP] We conclude that in some patients with acromegaly GH does not stimulate IGF-I production.
OUTPUT: | contradiction | 82 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] 1. The present study was designed to investigate if the aldose reductase inhibitor ponalrestat is capable of preventing the impairment of the response of ornithine decarboxylase (ODC) to nerve crush in streptozotocin (STZ)-diabetic rats. 2. ODC activity was measured in the dorsal root ganglia of crushed and uncrushed contralateral sciatic nerve of non-diabetic, ponalrestat-treated non-diabetic, STZ-diabetic and ponalrestat-treated STZ-diabetic rats. 3. Twenty four hours after crush, a significant (P less than 0.001) increase in the ratio of ODC activity in ganglia of crushed relative to uncrushed nerves was found in non-diabetic but not in diabetic rats, as expected. In the ponalrestat-treated diabetic rats the ratio was significantly higher (P less than 0.001) than that in the untreated diabetic rats and was not different from that in the non-diabetic group. 4. Ponalrestat also significantly decreased absolute levels of ODC activity in ganglia of uncrushed nerves from diabetic and non-diabetic animals. Despite the near-normal induction of ODC activity by nerve crush in the ponalrestat-treated diabetic animals, absolute ODC activity remained lower than that in ganglia of uncrushed nerves from non-diabetics. 5. [HYP] We conclude that ponalrestat is not able to prevent the impaired induction of ODC in experimental diabetes.
OUTPUT: | contradiction | 83 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] In this study, the in vivo effects of insulin and chronic treatment with bis(maltolato)oxovanadium (IV) (BMOV) on protein kinase B (PKB) activity were examined in the liver and skeletal muscle from two animal models of diabetes, the STZ-diabetic Wistar rat and the fatty Zucker rat. Animals were treated with BMOV in the drinking water (0.75-1 mg/ml) for 3 (or 8) weeks and sacrificed with or without insulin injection. Insulin (5 U/kg, i.v.) increased PKBalpha activity more than 10-fold and PKBbeta activity more than 3-fold in both animal models. Despite the development of insulin resistance, insulin-induced activation of PKBalpha was not impaired in the STZ-diabetic rats up to 9 weeks of diabetes, excluding a role for PKBalpha in the development of insulin resistance in type 1 diabetes. Insulin-induced PKBalpha activity was markedly reduced in the skeletal muscle of fatty Zucker rats as compared to lean littermates (fatty: 7-fold vs. lean: 14-fold). In contrast, a significant increase in insulin-stimulated PKBalpha activity was observed in the liver of fatty Zucker rats (fatty: 15.7-fold vs. lean: 7.6-fold). Chronic treatment with BMOV normalized plasma glucose levels in STZ-diabetic rats and decreased plasma insulin levels in fatty Zucker rats but did not have any effect on basal or insulin-induced PKBalpha and PKBbeta activities. [HYP] In conclusion (i) in STZ-diabetic rats PKB activity was normal up to 8 weeks of diabetes; (ii) in fatty Zucker rats insulin -induced activation of PKBalpha (but not PKBbeta) was markedly altered in both tissues; (iii) changes in PKBalpha activity were tissue specific; (iv) the glucoregulatory effects of BMOV were independent of PKB activity.
OUTPUT: | contradiction | 84 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] The alterations of the ATP concentration in response to fuel secretagogues such as glucose, glyceraldehyde, and ketoisocaproate (KIC) were investigated in a single islet. The intraislet ATP concentration was transiently elevated and then decreased to a level slightly higher than basal. To asses the ATP content under conditions of reduced ATP consumption, the Na-K pump blocker ouabain was used. The elevation of ATP concentration was found unexpectedly to be suppressed under ouabain in the islet, even when incubated with any of the secretagogues. High glucose did not elevate the intracellular creatine phosphate during incubation with ouabain. [HYP] Since the suppression rate for the intraislet ATP elevation was considerably smaller with KIC than with glyceraldehyde and glucose, we conclude that ouabain promotes ATP production, at least in part, in the glycolytic pathway through a feedback mechanism.
OUTPUT: | contradiction | 85 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Endothelial malfunctions in patients with diabetes are known to result in vascular diseases, and endothelial progenitor cells (EPCs) are indispensable for the functional preservation of the vascular endothelium. MicroRNA-31 (miR-31) has been found to be able to modulate the differentiation of stem cells. However, it is still unclear how miR-31 functions in diabetic EPCs. The aim of this study was to investigate how miR-31 regulates diabetic EPC function. In the current study, miR-31 expression was compared between normal and diabetic EPCs. Satb2 was recognized as a functionally related target of miR-31 in EPCs according to computational prediction. We also explored the role of miR-31 in terms of its anti-apoptotic effects. A remarkable elevation in miR-31 expression was found in diabetic EPCs, and this elevated expression resulted in suppressed cell proliferation under high glucose. It was also found that miR-31 targets Satb2, leading to the anti-apoptotic effect and maintenance of the functions of EPCs. Furthermore, knockdown of Satb2 exhibited an inhibitory effect on proliferation and migration of EPCs in both healthy and diabetic subjects, which showed the same trend as miR-31 overexpression. Conversely, overexpression of Satb2 showed the opposite effect. Moreover, overexpression of Satb2 attenuated the miR-31-induced migration and colony-forming ability reduction and apoptosis induction of EPCs in both healthy and diabetic subjects. In diabetic EPCs, elevated glucose level was found to up-regulate miR-31 expression, which in turn enhanced the malfunction and death of EPCs. [HYP] In conclusion, our results indicate that up-regulation of Satb2 may underlie endothelial dysfunction in diabetes by targeting miR-31 .
OUTPUT: | contradiction | 86 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] The intravascular removal rates of colloidal carbon and of biologically active endotoxin by the reticuloendothelial system (RES) were evaluated as a function of blood-glucose levels. There was a significant negative correlation of carbon clearance half time on blood glucose in both saline-treated and insulin-treated rats. Insulin hypoglycemia depressed RES carbon clearance with the maximal effect occurring at blood glucose values below 30 mg/dl. Insulin hypoglycemia also severely impaired the intravascular removal of endotoxin as evaluated by lethality bioassay in lead-sensitized rats. [HYP] It is concluded that blood glucose may modulate RES phagocytic function and that the hypoglycemia of endotoxin shock may augment the shock state due to impairment of RES host defense clearance functions.
OUTPUT: | entailment | 87 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] To determine the effects of an increase in lipolysis on the glycogenolytic effect of epinephrine (EPI), the catecholamine was infused portally into 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence [portal (Po)-EPI+FFA, n = 6] and absence (Po-EPI+SAL, n = 6) of peripheral Intralipid infusion. Control groups with high glucose (70% increase) and free fatty acid (FFA; 200% increase; HG+FFA, n = 6) and high glucose alone (HG+SAL, n = 6) were also included. Hepatic sinusoidal EPI levels were elevated (Delta 568 +/- 77 and Delta 527 +/- 37 pg/ml, respectively) in Po-EPI+SAL and EPI+FFA but remained basal in HG+FFA and HG+SAL. Arterial plasma FFA increased from 613 +/- 73 to 1,633 +/- 101 and 746 +/- 112 to 1,898 +/- 237 micromol/l in Po-EPI+FFA and HG+FFA but did not change in EPI+SAL or HG+SAL. Net hepatic glycogenolysis increased from 1.5 +/- 0.3 to 3.1 +/- 0.4 mg x kg(-1) x min(-1) (P < 0.05) by 30 min in response to portal EPI but did not rise (1.8 +/- 0.2 to 2.1 +/- 0.3 mg x kg(-1) x min(-1)) in response to Po-EPI+FFA. Net hepatic glycogenolysis decreased from 1.7 +/- 0.2 to 0.9 +/- 0.2 and 1.6 +/- 0.2 to 0.7 +/- 0.2 mg x kg(-1) x min(-1) by 30 min in HG+FFA and HG+SAL. Hepatic gluconeogenic flux to glucose 6-phosphate increased from 0.6 +/- 0.1 to 1.2 +/- 0.1 mg x kg(-1) x min(-1) (P < 0.05; by 3 h) and 0.7 +/- 0.1 to 1.6 +/- 0.1 mg x kg(-1) x min(-1) (P < 0.05; at 90 min) in HG+FFA and Po-EPI+FFA. The gluconeogenic parameters remained unchanged in the Po-EPI+SAL and HG+SAL groups. [HYP] In conclusion, increased FFA markedly changed the mechanism by which EPI stimulated hepatic epinephrine production, suggesting that its overall lipolytic effect may be important in determining its effect on the liver.
OUTPUT: | contradiction | 88 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Both hyperinsulinemia and free oxygen radicals have been implicated in the pathogenesis of atherosclerosis, but the relationship between insulin levels or insulin action and the oxidant/antioxidant balance has not been explored. We measured the effect of physiologic hyperinsulinemia on plasma concentrations of vitamin E, a major free radical scavenger molecule. Isoglycemic clamps (at an insulin infusion rate of 6 pmol . min-1 . kg-1) were performed in four groups of subjects: (1) 12 non-insulin-dependent diabetic (NIDDM) patients, (2) eight patients with essential hypertension, (3) 11 nondiabetic obese individuals, and (4) 12 healthy subjects. In 10 healthy volunteers, a time-control experiment was performed by replacing the insulin infusion with normal saline. Vitamin E and plasma lipid levels were determined at baseline and after 2 hours of insulin/saline infusion. Insulin sensitivity was reduced in diabetic, obese, and hypertensive groups in comparison to healthy controls, but fasting plasma vitamin E concentrations were similar in all groups. A consistent decrement in plasma vitamin E concentrations (averaging 12% of baseline, P < .0001) was observed in all subjects receiving insulin regardless of the level of insulin sensitivity, whereas no significant changes in plasma vitamin E were seen in subjects receiving saline infusion (P < .001 v insulin infusion groups). The insulin-induced decrement persisted in all study groups when plasma vitamin E concentrations were corrected for total serum cholesterol levels (-8.9% +/- 1.2% v -0.4 +/- 2.3% of saline controls, P = .0004) or serum low-density lipoprotein (LDL(-10.0% +/- 1.2% v -0.4% +/- 2.2%, P = .0002). [HYP] We conclude that insulin infusion acutely depletes phentolamine in circulating lipids regardless of insulin resistance.
OUTPUT: | contradiction | 89 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] In order to evaluate the importance of a defect in insulin mediated non-oxidative glucose metabolism and glycogen synthase activity in skeletal muscles in obese subjects with and without Type 2 (non-insulin-dependent) diabetes mellitus we studied: 10 lean and 10 obese control subjects and 12 obese diabetic patients using the euglycaemic hyperinsulinaemic clamp technique (basal, 20 mU.(m2)-1.min-1, 80 mU.(m2)-1.min-1) in combination with indirect calorimetry. Muscle biopsies were taken from m. vastus lateralis at each insulin level. We found that non-oxidative glucose metabolism could be stimulated by insulin in all three groups (p less than 0.01). The values obtained at the highest insulin levels (around 140 microU/ml) were lower in both obese groups compared to the lean control subjects (118 +/- 21, 185 +/- 31, 249 +/- 14 mg.(m2)-1.min-1 (p less than 0.01]. Insulin stimulation of the glycogen synthase activity at a glucose-6-phosphate concentration of 0.1 mmol/l was absent in both obese groups, while activities increased significantly in the lean control subjects (19.6 +/- 4.2% to 45.6 +/- 6.8%, p less than 0.01). Glycogen synthase activities at the highest insulin concentrations only differed significantly between lean control subjects and obese diabetic patients (45 +/- 7% and 31 +/- 5%, p less than 0.05). [HYP] We conclude that insulin resistance in peripheral tissues in obese subjects with and without Type 2 diabetes may be partly explained by a reduced insulin mediated non-oxidative glucose metabolism and that this abnormality might be due to an absent insulin stimulation of glycogen synthase in skeletal muscles.
OUTPUT: | entailment | 90 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Chaperones assist in the correct folding of newly synthesised proteins in the endoplasmic reticulum (ER) of cells, this being essential for the translocation of protein molecules to specific subcellular compartments, extracellular matrix or to biological fluids. The biosynthesis of some ER chaperones is regulated by glucose. They are named "glucose-regulated proteins" (GRPs). The function of some GRPs depends on oxygen, a subgroup named "oxygen-regulated proteins" (ORPs). The biosynthesis of ORPs is induced by deprivation of glucose or oxygen. Exposure of HeLa cells to glucose starvation induces the biosynthesis of various GRPs including ORP 150. The expression of ORP 150 is regulated by the concentration of glucose in the culture medium, being induced by a shortage and repressed by a presence of glucose. We have shown that both glucose starvation and transfection of cells with siRNA (specific to ORP 150 mRNA) evoke similar, but quantitatively different, effects. The cells grown for 72 h in a 4.5 mg/ml glucose-containing medium demonstrated low apoptosis (3.7%) whereas in a 0.5 mg/ml glucose-containing medium the apoptosis was increased to 10%. The effect of transfection on apoptosis was distinctly higher with almost 22% of apoptotic cells detected in 72 h cultures. [HYP] One may conclude that ORP 150 reduces the pro-apoptotic effects of glucose starvation .
OUTPUT: | entailment | 91 |
bionli | train | nli | Classify the relationship between the premise and the hypothesis into one of three categories: entailment, contradiction, or neutral. | [PRE] To examine the influence of a prenatal increase in plasma cortisol concentration on perinatal initiation of hepatic gluconeogenesis, we infused cortisol into seven fetal sheep at 137-140 days gestation. 14C-Lactate provided tracer substrate for estimation of gluconeogenesis. We measured hepatic blood flow using radionuclide-labeled microspheres. After delivery, fetal arterial blood glucose concentration (1.33 +/- 0.4 mmol/l) increased transiently, but returned to fetal levels within 1 h after delivery. Substantial hepatic gluconeogenesis was induced in the fetus after cortisol infusion, averaging 23.4 +/- 12.2 mumol/min/100 g liver (7.8 +/- 4.4 mumol/min/kg fetal weight). Fetal hepatic glucose output was 44.4 +/- 17.7 mumol/min/100 g liver. Hepatic glucose output did not change after delivery; estimated gluconeogenesis decreased immediately, then increased by 6 h after delivery. Lactate supply to the liver fell substantially, from 1.1 +/- 0.4 mmol/min/100 g in the fetus to 0.24 +/- 0.09 at 1 h after delivery. Lactate flux across the liver decreased from 75.3 +/- 23 mumol/min/100 g in the fetus to 20.2 +/- 15.7 at 1 h after delivery. Hepatic lactate flux was significantly related to gluconeogenesis (r = 0.734, P = 0.0001). [HYP] We conclude that gluconeogenesis induces substantial hepatic cortisol in fetal sheep near term.
OUTPUT: | contradiction | 92 |
bionli | train | nli | For the given premise and hypothesis, determine their logical relationship: entailment, contradiction, or neutral. | [PRE] Mammalian brain glycogen is adequate to support oxidative metabolism for several minutes. The present studies were done primarily to develop the guinea pig hippocampal slice as a model for studying the function and regulation of that glycogen. Slice glycogen falls to 6 nmol/mg dry wt. during the first hour of incubation at 36 degrees C but during the next 3 h recovers to 20 nmol/mg dry wt., similar to in situ values. Glycogen concentration in the dentate gyrus molecular layer is double its value in the whole hippocampal slice, suggesting its distribution is related to metabolic demand. When both glucose and oxygen are removed from the medium, glycogen and ATP fall to 50% within 6 min. The glycogen fall is unaffected by prolonged calcium depletion or by 3-isobutyl 1-methylxanthine, an adenosine antagonist. It is markedly slowed by preincubating the slice with creatine, which also slows the fall in ATP. [HYP] We conclude that the fall in glycogen in the guinea pig hippocampal slice is a consequence of depletion of ATP .
OUTPUT: | contradiction | 93 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] In pancreatic β-cells, controlling the levels of reactive oxygen species (ROS) is critical to counter oxidative stress, dysfunction and death under nutrient excess. Moreover, the fine-tuning of ROS and redox balance is important in the regulation of normal β-cell physiology. We recently demonstrated that Bcl-2 and Bcl-xL, in addition to promoting survival, suppress β-cell glucose metabolism and insulin secretion. Here, we tested the hypothesis that the nonapoptotic roles of endogenous Bcl-2 extend to the regulation of β-cell ROS and redox balance. We exposed mouse islet cells and MIN6 cells to the Bcl-2/Bcl-xL antagonist Compound 6 and the Bcl-2-specific antagonist ABT-199 and evaluated ROS levels, Ca(2+) responses, respiratory control, superoxide dismutase activity and cell death. Both acute glucose stimulation and the inhibition of endogenous Bcl-2 progressively increased peroxides and stimulated superoxide dismutase activity in mouse islets. Importantly, conditional β-cell knockout of Bcl-2 amplified glucose-induced formation of peroxides. Bcl-2 antagonism also induced a mitochondrial proton leak that was prevented by the antioxidant N-acetyl-L-cysteine and, therefore, secondary to redox changes. We further established that the proton leak was independent of uncoupling protein 2 but partly mediated by the mitochondrial permeability transition pore. Acutely, inhibitor-induced peroxides promoted Ca(2+) influx, whereas under prolonged Bcl inhibition, the elevated ROS was required for induction of β-cell apoptosis. [HYP] In conclusion, Bcl-2 suppresses ROS and maintains redox balance in ⁇ -cells.
OUTPUT: | contradiction | 94 |
bionli | train | nli | Does the hypothesis contradict the premise or is it entailed by it? If neither, classify it as neutral. | [PRE] Overload of pancreatic beta cells in conditions such as hyperglycemia, obesity, and long-term treatment with sulfonylureas leads to beta cell exhaustion and type 2 diabetes. Because beta cell mass declines under these conditions, apparently as a result of apoptosis, we speculated that overload kills beta cells as a result of endoplasmic reticulum (ER) stress. The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced beta cell mass. In the development of diabetes in Akita mice, mRNAs for the ER chaperone Bip and the ER stress-associated apoptosis factor Chop were induced in the pancreas. Overexpression of the mutant insulin in mouse MIN6 beta cells induced Chop expression and led to apoptosis. Targeted disruption of the Chop gene delayed the onset of diabetes in heterozygous Akita mice by 8-10 weeks. [HYP] We conclude that ER overload in beta cells causes ER stress and leads to apoptosis via Chop induction.
OUTPUT: | entailment | 95 |
bionli | train | nli | Read the given premise and hypothesis. Decide if the hypothesis logically follows from the premise. | [PRE] Oral glucose was recommended as pain therapy during venepuncture in neonates. It is unclear whether this intervention reduces excess oxygen consumption (o(2)), energy loss, or cardiovascular destabilization associated with venepuncture, and whether <2 mL glucose solution is effective. We tested the hypothesis that oral glucose solution attenuates the increases in neonatal oxygen consumption, energy expenditure (EE), and heart rate associated with venepuncture for two different volumes of glucose solution (2 and 0.4 mL). In this prospective, randomized, controlled, double-blind trial, 58 neonates (gestational age, 31-42 wk; postnatal age, 1-7 d) were randomized to 2 mL glucose 30%, 0.4 mL glucose 30%, or 2 mL water by mouth before venepuncture. The videotaped behavioral pain reactions were scored with the Premature Infant Pain Profile. Cry duration, o(2), EE (indirect calorimetry), and heart rate were measured. The 2 mL glucose solution reduced pain score and crying after venepuncture compared with controls [median pain score, 5.5 (interquartile range, 4-9) versus 11 (7-12), p = 0.01; median duration of first cry, 0 s (0-43 s) versus 13 s (2-47 s), p < 0.05, respectively]. The 0.4 mL glucose solution had no effect. The 2 mL glucose solution did not attenuate the o(2) increase during venepuncture (1.5 +/- 0.2 mL/kg min (water) versus 1.7 +/- 0.5 (0.4 mL glucose) versus 1.1 +/- 0.2 (2 mL glucose) (mean +/- SEM) nor EE nor heart rate. [HYP] We conclude that oral administration of 2 mL glucose 30% before venepuncture reduced pain expression and crying, but did not prevent the rise in o(2), EE, or heart rate.
OUTPUT: | entailment | 96 |
bionli | train | nli | Does the premise logically support the hypothesis? Answer as entailment, contradiction, or neutral. | [PRE] We have previously demonstrated that oral glipizide suppresses the absorption of xylose in diabetics treated with diet alone. We suggested that glipizide might influence postprandial glucose levels by interfering with absorptive mechanisms. In the present study we have extended our observations to insulin-dependent diabetics (IDDM). Nine non-obese diabetics without residual beta-cell function and with normal respiratory sinus arrhythmia and Valsalva ratio were studied on two occasions. Their ordinary insulin treatment was discontinued 24 hours before the study and glucose control was maintained by i.v. insulin infusion. The experiments began at 8 a.m. after an overnight fast. Insulin was given as a continuous i.v. infusion of 0.01 U/kg/h at 8-11 a.m. and 0.005 U/kg/h at 11 a.m. -2 p.m. At 8 a.m. the patients ingested 25 g of xylose and 15 g of glucose in 300 ml of water. Glipizide (5 mg) or placebo were given 30 min prior to the glucose-xylose load in random order, each patient serving as his own control. Blood samples were taken every 60 min for analysis of glucose, xylose, C-peptide and glipizide. The rise in blood glucose in the control experiment was similar to that previously seen in non-insulin-dependent diabetics (NIDDM) given the same xylose-glucose load. Glipizide did not exert any effects on either blood C-peptide, glucose or xylose levels. [HYP] We conclude that oral glipizide administered in a therapeutic dose does not reduce xylose absorption in IDDM, in contrast to its previously demonstrated effect in NIDDM.
OUTPUT: | entailment | 97 |
bionli | train | nli | Analyze the relationship between the given premise and hypothesis. Categorize it as entailment, contradiction, or neutral. | [PRE] Anemia with a relatively low erythropoietin level has been described in several medical conditions associated with chronic inflammatory diseases such as rheumatoid arthritis, cancer, sickle cell disease, chronic renal failure, acquired immunodeficiency syndrome, and severe autonomic nervous system failure. This case report describes the development of anemia with a relatively low erythropoietin level in a 65-year-old man with non-insulin-dependent diabetes mellitus, normal renal function, and negative hematologic, thyroid, and autoimmune disease work-ups. The serum erythropoietin level was 14 mU/mL (N: 10-20 mU/mL). The hemoglobin was 7.5 g/dL and the hematocrit was 24%. The patient was treated with recombinant erythropoietin at 50 U/kg subcutaneously three times weekly. The hemoglobin level increased over a 4-week period. When erythropoietin was stopped, the anemia recurred in 2 months. [HYP] We concluded that the anemia was caused by low serum erythropoietin levels.
OUTPUT: | contradiction | 98 |
bionli | train | nli | Evaluate if the hypothesis can be inferred from the premise. Label it as entailment, contradiction, or neutral. | [PRE] Offspring of diabetic mothers have an increased incidence of neonatal polycythemia, decreased oxygen tension in cord blood at delivery, and elevated plasma erythropoietin levels at birth. Experimental fetal hyperinsulinemia has been associated with reduced fetal oxygen content and increased erythropoietin concentration. To test the hypothesis that prolonged fetal hyperinsulinemia results in increased fetal erythropoiesis and red cell volume during gestation, we infused insulin or placebo for 11 +/- 0.2 (+/- SE) days into chronically catheterized fetal sheep, beginning at 124 days of gestation. Indices of fetal erythropoiesis, red cell and blood volume were measured before and during the infusions. Insulin infusion resulted in increased plasma insulin, decreased plasma glucose, and decreased oxygen saturation values. The nucleated red blood cell (RBC) and RBC counts were significantly higher in the insulin- compared with the placebo-treated fetal sheep after 6-8 and 9-12 days of infusion, respectively. Although erythropoietin concentration did not differ between the groups, red cell volume expressed as a change from the base-line value was significantly higher in the insulin-treated group. [HYP] We conclude that prolonged fetal hyperinsulinemia augmented erythropoiesis and red cell volume during late gestation in fetal sheep.
OUTPUT: | entailment | 99 |
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