Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lowering of the plasma FFA level in intact fasted rats by infusion of nicotinic acid (NA) caused essentially complete ablation of insulin secretion (IS) in response to a subsequent intravenous bolus of arginine, leucine, or glibenclamide (as previously found using glucose as the beta-cell stimulus). However, in all cases, IS became supranormal when a high FFA level was maintained by co-infusion of lard oil plus heparin. Each of these secretagogues elicited little, if any, IS from the isolated, perfused "fasted" pancreas when tested simply on the background of 3 mM glucose, but all became extremely potent when 0.5 mM palmitate was also included in the medium. Similarly, IS from the perfused pancreas, in response to depolarizing concentrations of KCl, was markedly potentiated by palmitate. As was the case with intravenous glucose administration, fed animals produced an equally robust insulin response to glibenclamide regardless of whether their low basal FFA concentration was further reduced by NA. In the fasted state, arginine-induced glucagon secretion appeared to be independent of the prevailing FFA concentration. The findings establish that the essential role of circulating FFA for glucose-stimulated IS after food deprivation also applies in the case of nonglucose secretagogues. In addition, they imply that (i) a fatty acid-derived lipid moiety, which plays a pivotal role in IS, is lost from the pancreatic beta-cell during fasting; (ii) in the fasted state, the elevated level of plasma FFA compensates for this deficit; and (iii) the lipid factor acts at a late step in the insulin secretory pathway that is common to the action of a wide variety of secretagogues.
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PMID:A fatty acid- dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion. 961 8

This study examined the effect of reduced plasma free fatty acid (FFA) availability on carbohydrate metabolism during exercise. Six untrained women cycled for 60 minutes at approximately 58% of maximum oxygen uptake after ingestion of a placebo (CON) or nicotinic acid (NA), 30 minutes before exercise (7.4 +/- 0.5 mg.kg(-1) body weight), and at 0 minutes (3.7 +/- 0.3 mg.kg(-1)) and 30 minutes (3.7 +/- 0.3 mg.kg(-1)) of exercise. Glucose kinetics were measured using a primed, continuous infusion of [6,6-(2)H] glucose. Plasma FFA (CON, 0.86 +/- 0.12; NA, 0.21 +/- 0.11 mmol.L(-1) at 60 minutes, P <.05) and glycerol (CON, 0.34 +/- 0.05; NA, 0.10 +/- 0.04 mmol.L(-1) at 60 minutes, P <.05) were suppressed throughout exercise. Mean respiratory exchange ratio (RER) during exercise was higher (P <.05) in NA (0.89 +/- 0.02) than CON (0.83 +/- 0.02). Plasma glucose and glucose production were similar between trials. Total glucose uptake during exercise was greater (P <.05) in NA (1,876 +/- 161 micromol.kg(-1)) than in CON (1,525 +/- 107 micromol.kg(-1)). Total fat oxidation was reduced (P <.05) by approximately 32% during exercise in NA. Total carbohydrate oxidized was approximately 42% greater (P <.05) in NA (412 +/- 40 mmol) than CON (290 +/- 37 mmol), of which, approximately 16% (20 +/- 10 mmol) could be attributed to glucose. Plasma insulin and glucagon were similar between trials. Catecholamines were higher (P <.05) during exercise in NA. In summary, during prolonged moderate exercise in untrained women, reduced FFA availability results in a compensatory increase in carbohydrate oxidation, which appears to be due predominantly to an increase in glycogen utilization, although there was a small, but significant, increase in whole body glucose uptake.
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PMID:Carbohydrate metabolism during exercise in females: effect of reduced fat availability. 1128 47

Increased circulating free fatty acids (FFAs) inhibit both hepatic and peripheral insulin action. Because the loss of effectiveness of glucose to suppress endogenous glucose production and stimulate glucose uptake contributes importantly to fasting hyperglycemia in type 2 diabetes, we examined whether the approximate twofold elevations in FFA characteristic of poorly controlled type 2 diabetes contribute to this defect. Glucose levels were raised from 5 to 10 mmol/l while maintaining fixed hormonal conditions by infusing somatostatin with basal insulin, glucagon, and growth hormone. Each individual was studied at two FFA levels: with (NA+) and without (NA-) infusion of nicotinic acid in nine individuals with poorly controlled type 2 diabetes (HbA(1c) = 10.1 +/- 0.7%) and with (LIP+) and without (LIP-) infusion of lipid emulsion in nine nondiabetic individuals. Elevating FFA to approximately 500 micro mol/l blunted the ability of glucose to suppress endogenous glucose production (LIP- = -48% vs. LIP+ = -28%; P < 0.01) and increased glucose uptake (LIP- = 97% vs. LIP+ = 51%; P < 0.01) in nondiabetic individuals. Raising FFA also blunted the endogenous glucose production response in 10 individuals with type 2 diabetes in good control (HbA(1c) = 6.3 +/- 0.3%). Conversely, normalizing FFA nearly restored the endogenous glucose production (NA- = -7% vs. NA+ = -41%; P < 0.001) and glucose uptake (NA- = 26% vs. NA+ = 64%; P < 0.001) responses to hyperglycemia in individuals with poorly controlled type 2 diabetes. Thus, increased FFA levels contribute substantially to the loss of glucose effectiveness in poorly controlled type 2 diabetes.
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PMID:Contribution of elevated free fatty acid levels to the lack of glucose effectiveness in type 2 diabetes. 1457 93

We used tracer and arteriovenous difference techniques in conscious dogs to determine the effect of nonesterified fatty acids (NEFAs) on net hepatic glucose uptake (NHGU). The protocol included equilibration ([3-(3)H]glucose), basal, and two experimental periods (-120 to -30, -30 to 0, 0-120 [period 1], and 120-240 min [period 2], respectively). During periods 1 and 2, somatostatin, basal intraportal insulin and glucagon, portal glucose (21.3 micromol.kg(-1).min(-1)), peripheral glucose (to double the hepatic glucose load), and peripheral nicotinic acid (1.5 mg.kg(-1).min(-1)) were infused. During period 2, saline (nicotinic acid [NA], n = 7), lipid emulsion (NA plus lipid emulsion [NAL], n = 8), or glycerol (NA plus glycerol [NAG], n = 3) was infused peripherally. During period 2, the NA and NAL groups differed (P < 0.05) in rates of NHGU (10.5 +/- 2.08 and 4.7 +/- 1.9 micromol.g(-1).min(-1)), respectively, endogenous glucose R(a) (2.3 +/- 1.4 and 10.6 +/- 1.0 micromol.kg(-1).min(-1)), net hepatic NEFA uptakes (0.1 +/- 0.1 and 1.8 +/- 0.2 micromol.kg(-1).min(-1)), net hepatic beta-hydroxybutyrate output (0.1 +/- 0.0 and 0.4 +/- 0.1 micromol.kg(-1).min(-1)), and net hepatic lactate output (6.5 +/- 1.7 vs. -2.3 +/- 1.2 micromol.kg(-1).min(-1)). Hepatic glucose uptake and release were 2.6 micro mol. kg(-1). min(-1) less and 3.5 micro mol. kg(-1). min(-1) greater, respectively, in the NAL than NA group (NS). The NAG group did not differ significantly from the NA group in any of the parameters listed above. In the presence of hyperglycemia and relative insulin deficiency, elevated NEFAs reduce NHGU by stimulating hepatic glucose release and suppressing hepatic glucose uptake.
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PMID:Nonesterified fatty acids and hepatic glucose metabolism in the conscious dog. 1469 95


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