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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acids glycine, L-serine, L-asparagine and L-glutamine at 5 mmol/l each markedly increased glucagon release from perifused fetal lamb pancreas tissue, whereas the branched-chain amino acids L-leucine and L-valine had no effect. In contrast, only L-leucine and L-valine had any effect on insulin release. With perifused pancreas tissue from newborn lambs (5-9 days of age) glycine, L-serine, L-asparagine, L-arginine and L-lysine caused a similar marked increase in glucagon secretion with glycine having the greatest effect. These stimulatory effects were attenuated little by addition of glucose (20 mmol/l). L-Leucine had little effect on glucagon release, but was the only amino acid tested which caused marked insulin release in the absence of glucagon. Continuous intravenous infusion of glutamine (3 mmol/h per kg estimated fetal weight) or glutamine and asparagine each at this rate for 2 h into chronically cannulated fetal sheep in utero significantly increased plasma glucagon (P less than 0.05) and insulin (P less than 0.01) concentrations, although the effect on glucagon was not great. The results show how a range of amino acids can influence glucagon and insulin release from the pancreas of fetal and newborn lambs suggesting that physiological changes in plasma amino acid concentrations may contribute to regulation of glucagon and insulin release in utero in this species.
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PMID:Glucagon and insulin release in the lamb before and after birth: effects of amino acids in vitro and in vivo. 676 31

The present study was designed to examine the effects of excess T3 on total body glucose production and forearm exchange of glucose, amino acids, and other metabolites. Five healthy male volunteers were studied after an overnight fast, before and 7 days after the administration of 150 micrograms/day T3. Glucose production (milligrams per kg/min) was measured using a primed continuous infusion of [3-3H]glucose and gluconeogenic index (micromoles per kg/min) was measured by following the conversion of infused [14C]alanine to [14C]glucose. Blood flow across the forearm was measured using capacitance plethysmography and forearm release of substrates was determined by the Fick principle. After T3 administration, there was a 3.7-fold rise in T3 from 150 +/- 15 to 530 +/- 12 ng/dl (P less than 0.001), with no change in insulin (12 +/- 1 microU/ml pre-T3 vs. 13 +/- 2 microU/ml post-T3) and glucagon (79 +/- 5 pre-T3 vs. 84 +/- 7 pg/ml post-T3). T3 administration resulted in an increase in plasma glucose (from 83 +/- 5 to 98 +/- 5 mg/dl; P less than 0.05), net glucose uptake by the forearm (from 250 +/- 90 to 712 +/- 60 nmol/100 ml forearm tissue X min; P less than 0.005) and glucose production (1.7 +/- 0.09 to 2.2 +/- 0.08 mg/kg X min; P less than 0.005), without a change in glucose clearance (2.1 +/- 0.02 vs. 2.0 +/- 0.02 ml/kg X min); the rate of conversion of [14C]alanine to [14C]glucose increased by 30% (0.56 +/- 0.03 to 0.74 +/- 0.03 mumol/ kg X min P less than 0.005). These values were associated with a 25% increase in blood lactate to 712 +/- 69 mumol/liter (P less than 0.05) and a 131% increase in lactate release across the forearm to 434 +/- 90 (P less than 0.005). Forearm release of alanine (96 +/- 29 nmol/100 ml forearm tissue X min) and glutamine (151 +/- 41 nmol/100 ml forearm tissue X min) increased by 90% (P less than 0.005 and P = 0.04, respectively), with no change in their concentrations. Forearm release of branched chain amino acids did not change, while those of their ketoacids, alpha-ketoisocaproate (KIC) and alpha-ketoisovalerate (KIV), doubled (to 64 +/- 9 mumol/liter for KIC and 39 +/- 6 mumol/liter for KIV; P less than 0.05). These were associated with a 45% increase in the branched chain amino acid levels and a 46% rise in both KIC and KIV levels to 41 +/- 9 and 28 +/- 7 mumol/liter, respectively (P less than 0.05). There was a concurrent significant (P less than 0.05) change in the arterial levels of phenylalanine (-32%), tyrosine (-29%), threonine (-20%), glycine (-20%), and serine (-15%), without any change in their efflux across the forearm. The data indicate that a pharmacologically induced rise in T3, to levels comparable to those seen in hyperthyroidism, results in enhanced glucose production, with an increase in glucose uptake by the forearm. The former can be partially accounted for by an increase in hepatic gluconeogenesis, glycogenolysis, or possibly increased renal glucose production...
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PMID:The effect of thyroid hormones on gluconeogenesis and forearm metabolism in man. 682 48

Studies were conducted to determine whether the direction of hepatic carbohydrate and lipid metabolism in the rat could be switched simultaneously from a "fasted" to a "fed" profile in vitro. When incubated for 2 h under appropriate conditions hepatocytes from fasted animals could be induced to synthesize glycogen at in vivo rates. There was concomitant marked elevation of the tissue malonyl-coenzyme A level, acceleration of fatty acid synthesis, and suppression of fatty acid oxidation and ketogenesis. In agreement with reports from some laboratories, but contrary to popular belief, glucose was not taken up efficiently by the cells and was thus a poor substrate for eigher glycogen synthesis or lipogenesis. The best precursor for glycogen formation was fructose, whereas lactate (pyruvate) was most efficient in lipogenesis. In both case the addition of glucose to the gluconeogenic substrates was stimulatory, the highest rates being obtained with the further inclusion of glutamine. Insulin was neither necessary for, nor did it stimulate, glycogen deposition or fatty acid synthesis under favorable substrate conditions. Glucagon at physiological concentrations inhibited both glycogen formation and fatty acid synthesis. Insulin readily reversed the effects of glucagon in the submaximal range of its concentration curve. The following conclusions were drawn. First, the fasted-to-fed transition of hepatic carbohydrate and lipid metabolism can be accomplished in vitro over a time frame similar to that operative in vivo. Second, reversal appears to be a substrate-driven phenomenon, in that insulin is not required. Third, unless an unidentified factor (present in protal blood during feeding) facilitates the uptake of glucose by liver it seems unlikely that glucose is the immediate precursor for liver glycogen or fat synthesis in vivo. A likely candidate for the primary substrate in both processes is lactate, which is rapidly formed from glucose by the small intestine and peripheral tissues. Fructose and amino acids may also contribute. Fourth, the requirement for insulin in the reversal of the fasting state of liver metabolism in vivo can best be explained by its ability to offset the catabolic actions of glucagon.
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PMID:In vitro reversal of the fasting state of liver metabolism in the rat. Reevaluation of the roles of insulin and glucose. 701 43

Ammonium salts were infused in intact, pancreatectomized, and adrenalectomized dogs to produce coma-inducing amounts of plasma ammonia. Changes in intact dogs included hyperglycemia, hyperglucagonemia, hyperinsulinemia, and decreases in plasma concentrations of glutamine, alanine, threonine, glycine, lysine, valine, proline, serine, arginine, leucine, isoleucine, and methionine. Urinary excretion of catecholamines increased more than 20-fold, whereas plasma hydrocortisone concentrations were essentially unchanged. In pancreatectomized dogs, ammonia infusions caused hyperglycemia, a mild hyperglucagonemia, and no changes in plasma amino acid concentrations, other than a decrease in alanine and an increase in taurine. In adrenalectomized dogs, ammonia infusion resulted in normoglycemia, hyperglucagonemia (comparable with that seen in intact dogs), hyperinsulinemia (2 to 3 times that seen in intact dogs), and decreased plasma concentrations of alanine, isoleucine, leucine, and valine. Finally, propranolol administration did not affect ammonia-induced glucagon and insulin release. The endocrine portion of the pancreas appears to mediate the major effects of ammonia on plasma amino acid values. The effect of ammonia in stimulating glucagon release may occur by an alpha-adrenergic pathway or by direct stimulation of pancreatic islet cells.
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PMID:Effects of ammonia infusion on plasma glucagon, insulin, and amino acids in intact, pancreatectomized, and adrenalectomized dogs. 702 May

To determine whether the differences in fasting glucose responses in men, women and children could be related to differences in glucoregulatory hormone secretion or availability of circulating gluconeogenic substrates, 20 adults (10 men and 10 women) were fasted for 86 hr and 15 children (6.1 +/- 0.8 yr, mean +/- SE) were fasted for 30 hr. Circulating concentrations of glucose, ketone bodies, potential gluconeogenic substrates and glucoregulatory hormones were determined at frequent intervals. In the postprandial state (1-14 hr fasting), substrate and hormone concentrations were similar in all groups with the exception of plasma glutamine concentrations which were higher in men (640 +/- 20 microM) than in women of children (490 +/- 20 microM and 480 +/- 50 microM, respectively, p less than 0.01 for both). Following 30 hr fasting children had the lowest glucose (53 +/- 3 mg/dl) and alanine (167 +/- 17 microM) concentrations and men had the highest (72 +/- 3 mg/dl and 279 +/- 16 microM, respectively) whereas those of women were intermediate (64 +/- 3 mg/dl and 226 +/- 19 microM. respectively). Following 30 hr of fasting betahydroxybutyrate concentrations were highest in children and lowest in men (the children, 3.7 +/- 0.4 mM; women, 1.7 +/- 0.2 mM and men 0.9 +/- 0.2 mM, p less than 0.02 between all groups). An inverse relationship (p less than 0.001 was observed between beta-hydroxybutyrate and glucose concentrations throughout the fast for each group (r greater than 0.92). Although plasma cortisol concentrations were higher in women and children when compared to those of the men, no differences in growth hormone, glucagon, or insulin concentrations were observed among the three groups studied. Differences in plasma substrate responses to fasting among the groups studied may reflect differences in glucose requirements among men, women and children, as well as the relative availability of both gluconeogenic substrate and ketone bodies.
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PMID:Differences in circulating gluconeogenic substrates during short-term fasting in men, women, and children. 704 60

Vasopressin, angiotensin II, glucagon and epinephrine (through a cAMP-independent, alpha1adrenergic mechanism), stimulate ureogenesis in isolated rat hepatocytes. Mitochondria, isolated from hepatocytes which were previously treated with these hormones, displayed an enhanced rate of citrulline synthesis in the presence of NH4Cl as the nitrogen source. When mitochondria were incubated with glutamine as the nitrogen source, only those mitochondria isolated from hepatocytes previously treated with epinephrine or glucagon displayed an enhanced capacity to synthesize citrulline. When cells were incubated in the absence of extracellular calcium, the effects of vasopressin and angiotensin II on urea synthesis were abolished, whereas those of epinephrine and glucagon were only diminished. Mitochondria isolated from cells incubated under these conditions, showed that the effect of all these hormones on citrulline synthesis could still be observed. However, the effects of glucagon and epinephrine plus propranolol were larger than those of angiotensin II or vasopressin. Phosphatidylinositol labeling was significantly increased by epinephrine, vasopressin and angiotensin II both in the absence or presence of calcium. Cyclic AMP levels were significantly increased by glucagon or epinephrine but not by vasopressin or angiotensin II. The effect of epinephrine on cyclic AMP levels was blocked by propranolol both in the absence or presence of calcium.
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PMID:Vasopressin and angiotensin II stimulate ureogenesis through increased mitochondrial citrulline production. 715 49

Acute hepatic ischaemia was induced in pigs by means of a portacaval shunt with hepatic artery ligation after 24 hours. Despite significant elevation in blood ammonia, fatty acids, aspartate aminotransferase, cerebrospinal fluid glutamine and ammonia, and brain tissue glutamine, ammonia and tryptophan, the experimental animals remained awake and alert and indistinguishable from sham-operated controls. The molar ratio of branched-chain to aromatic amino acids fell sharply in the arterial blood, but showed a terminal attempt at compensation in muscle venous samples. Portal and muscle venous insulin levels were elevated, and glucagon values rose in all circulation segments in the experimental group. The failure to induce coma in these pigs, despite the presence of many of the classical biochemical features, suggests that the syndrome of encephalopathy comprises several stages, and that the pig may be an important model in which to define these.
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PMID:Acute hepatic ischaemia in the pig- the changes in plasma hormones, amino acids and brain biochemistry. 725 Aug 93

Hepatic amino acid contents were determined at time-points regularly spaced over a light-dark cycle in rats fed either a 12% casein diet or a single daily meal given 2 hours after the onset of the light phase with a protein-free diet and libitum. In mixed-fed rats, non-essential amino acid hepatic content remained stable over 24 hours while that of essential amino acids rose during the early part of the night in connection with the onset of prandial activity, but long before portal levels increased. The possibility of factors related to food intake (insulin, glucagon, gastrointestinal hormones) or to its chronology (corticoids) stimulating active transport is discussed. In separately-fed rats, amino acid pools increased in the 30 minutes following protein administration in connection with rising portal levels. During the rest of the light phase, a general depletion of non-essential amino acids occurred. It was most rapid for glutamine, alanine and aspartic acid and was followed by accumulation during the night phase, a pattern fitting well with gluconeogenesis and ureogenesis stimulation following protein ingestion. Essential amino acid decrease was linear and spanned over both the light and dark phases in correlation with decreasing portal levels.
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PMID:Circadian variations of liver free amino acid content in mixed-fed and protein-meal-fed rats. 727 33

Diurnal variation in hepatic levels of lactate, pyruvate, phosphoenolpyruvate (PEP), alpha-ketoglutarate, malate, oxaloacetate, ketone bodies, alanine, serine, glycine, aspartate, glutamate, glutamine, valine, urea, adenine nucleotides and inorganic phosphate were studied in rats adapted to a high protein, carbohydrate-free diet for 24 days. Most circadian rhythms differed in relation to controls (10% protein diet); many merely had different amplitudes, some were inverted, and some exhibited drastically altered patterns. Cytoplasmic redox state exhibited nearly similar variations and phosphorylation state differed primarily in amplitude whereas mitochondrial redox state was highly depressed in the absorptive phase. The metabolic regulation implied by the results is discussed in relation to both circadian variations of plasma insulin and glucagon concentrations, and pyruvate kinase and phosphoenolpyruvate carboxykinase activities previously reported.
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PMID:Circadian variation of liver metabolites and amino acids in rats adapted to a high protein, carbohydrate-free diet. 728 96

1. Injection of rats with glucagon leads to an increased effective activity of glutaminase in subsequently isolated liver mitochondria. 2. This effect of glucagon is manifested as a decreased requirement of glutaminase for phosphate in the presence of HCO3-. The HCO3--concentration-dependence is unchanged. 3. The effect of glucagon is lost on disruption of the mitochondria. 4. In accordance with previous reports, incubation of mitochondria in hypo-osmotic media also increases the effective activity of glutaminase. Glucagon increases glutamine hydrolysis at intermediate osmolarities of the suspending medium, but does not affect glutaminase activity when it is already maximally activated by hypo-osmotic conditions. 5. From this and previous work, it seems that hypo-osmotic incubation conditions, EDTA and glucagon may all activate glutaminase by a common mechanism. It is postulated that this mechanism involves modification of the interaction of glutaminase with the mitochondrial inner membrane.
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PMID:Increased activity of phosphate-dependent glutaminase in liver mitochondria as a result of glucagon treatment of rats. 730 82


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