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)

Hepatic phenylalanine(histidine):pyruvate aminotransferase activity is much higher in the mouse and rat than in other animal species (human, guinea-pig, rabbit, pig, dog and chicken). The activity is elevated in the mouse and rat by the injection of glucagon but not in other species (guinea-pig, rabbit and chicken). The enzyme was purified from the mitochondrial fraction of mouse liver to homogeneity as judged by polyacrylamide disc gel electrophoresis in the presence of dodecylsulphate. With histidine as amino donor, the enzyme was active with pyruvate, oxaloacetate and hydroxypyruvate as amino acceptors but not with 2-oxoglutarate. Effective amino donors were histidine, phenylalanine and tyrosine with pyruvate, and methionine, serine and glutamine with phenylpyruvate. The apparent Km for histidine was about 6.9 mM with pyruvate and that for pyruvate was 21 mM with histidine. The enzyme is probably composed of two identical subunits with a molecular weight of approximately 40000. The pH optimum was near 9.0. Isoelectric focusing of the purified enzyme resulted in the detection of four forms with pI 6.0, 6.2, 6.5 and 6.7, respectively, all of which were responsive to glucagon. These four forms were nearly identical with the purified enzyme before the focusing with respect to physical and enzymic properties. A possible mechanism of this multiplicity is discussed.
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PMID:Species distribution and properties of hepatic phenylalanine (histidine):pyruvate aminotransferase. 1 70

It is proposed that hyperammonaemia in liver cirrhosis or after portacaval shunt contributes to plasma neutral aminoacid imbalance and to increased activity of the blood-brain neutral amino-acid transport system. Plasma neutral aminoacid concentrations are deranged, partly, but not completely, because ammonia stimulates glucagon secretion; a high rate of gluconeogenesis and hyperinsulinaemia follow. Brain uptake of neutral aminoacids rises because ammonia stimulates brain-glutamine synthesis, which results in rapid exchange of brain glutamine for plasma neutral aminoacids. Hyperammonaemia therefore contributes to encephalopathy indirectly, by raising the brain concentration of neutral aminoacids which after neurotransmitter metabolism, rather than directly, by toxic effects on neuronal metabolism.
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PMID:Hyperammonaemia, plasma aminoacid imbalance, and blood-brain aminoacid transport: a unified theory of portal-systemic encephalopathy. 9 Aug 64

1. Hepatocytes from starved rats or fed rats whose glycogen content was previously depleted by phlorrhizin or by glucagon injections, form glycogen at rapid rates when incubated with 10mM-glucose, gluconeogenic precursors (lactate, glycerol, fructose etc.) and glutamine. There is a net synthesis of glucose and glycogen. 14C from all three types of substrate is incorporated into glycogen, but the incorporation from glucose represents exchange of carbon atoms, rather than net incorporation. 14C incorporation does not serve to measure net glycogen synthesis from any one substrate. 2. With glucose as sole substrate net glucose uptake and glycogen deposition commences at concentrations of about 12--15mM. Glycogen synthesis increases with glucose concentrations attaining maximal values at 50--60mM, when it is similar to that obtained in the presence of 10mM glucose and lactate plus glutamine. 3. The activities of the active (a) and total (a+b) forms of glycogen synthase and phosphorylase were monitored concomitant with glycogen synthesis. Total synthase was not constant during a 1 h incubation period. Total and active synthase activity increased in parallel with glycogen synthesis. 4. Glycogen phosphorylase was assayed in two directions, by conversion of glycose 1-phosphate into glycogen and by the phosphorylation of glycogen. Total phosphorylase was assyed in the presence of AMP or after conversion into the phosphorylated form by phosphorylase kinase. Results obtained by the various methods were compared. Although the rates measured by the procedures differ, the pattern of change during incubation was much the same. Total phosphorylase was not constant. 5. The amounts of active and total phosphorylase were highest in the washed cell pellet. Incubation in an oxygenated medium, with or without substrates, caused a prompt and pronounced decline in the assayed amounts of active and total enzyme. There was no correlation between phosphorylase activity and glycogen synthesis from gluconeogenic substrates. With fructose, active and total phosphorylase activities increased during glycogen syntheses. 6. In glycogen synthesis from glucose as sole substrate there was a decline in phosphorylase activities with increased glucose concentration and increased rates of glycogen deposition. The decrease was marked in cells from fed rats. 7. To determine whether phosphorolysis and glycogen synthesis occur concurrently, glycogen was prelabelled with [2-3H,1-14C]-galactose. During subsequent glycogen deposition there was no loss of activity from glycogen in spite of high amounts of assayable active phosphorylase.
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PMID:Glycogen synthesis by rat hepatocytes. 11 69

Two groups (each of 6 moderately ill, protein-depleted patients) were infused daily for 7 days. Mean 7 day nitrogen (N) balances with infusions of 0.83 and 1.83 g of a defined amino acid mixture (containing further nutrients but no other source of energy)/kg ideal body wt/day were -3.66 and +1.54 g/day, respectively (P less than 0.025) when adjusted for changes in body urea and estimated miscellaneous N losses. Concentrations of plasma free fatty acids, immunoreactive insulin and glucagon, and of blood glucose, pyruvate, lactate and glycerol were indistinguishable on corresponding treatment days in the 2 groups but blood ketone bodies were lower in the 1.83 g/kg group. Blood amino acid concentrations of alanine, valine, leucine, and isoleucine were similar, whereas those of phenylalanine, histidine, serine, and arginine were higher, and glutamine lower, in the 1.83 g/kg group. The data confirm that not only can body protein mass be maintained, but a net positive N retention achieved, in such patients, through provision of exogenous amino acids and concurrent mobilization of endogenous energy stores. Of note is that this fat mobilization can occur without plasma free fatty acids and/or significant blood ketone body elevations. An infusion of 2, rather than 1 g/kg/day seems suitable in the situation examined.
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PMID:Intravenous protein-sparing therapy in patients with gastrointestinal disease. 11 60

Hepatocytes prepared from streptozotocin- and alloxan-diabetic rats starved for 24 h contain 0.5--2% wet wt. of glycogen. Glycogen synthesis in the hepatocytes from such rats, after prior depletion of the glycogen by glucagon injection, was studied. As distinct from cells from normal animals, there was no glycogen synthesis from glucose as sole substrate, even at concentrations of 60 mM. When supplied with glucose, a gluconeogenic precursor (lactate, dihydroxyacetone or fructose), and with glutamine there was concurrent synthesis of glucose and of glycogen. Without glutamine there was little or no glycogen synthesis. The rate of glycogen formation was in the same range as for cells from control rats. Glutamine addition markedly activated glycogen synthase in cells of starved diabetic rats, but there was no effect on phosphorylase. We obtained very little synthesis of glycogen with hepatocytes from fed diabetic rats, whereas with normal animals, synthesis by such cells equals or exceeds that obtained from starved rats. The conversion of synthase b (inactive) into the active form was studied in rat liver homogenates. The activation of the synthase in cells from starved diabetic rats is somewhat less than that from normal animals, but that from fed diabetic rats is markedly decreased compared with that in livers of fed control animals or that of starved diabetic animals.
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PMID:Glycogen synthesis by hepatocytes from diabetic rats. 16 Feb 23

Alanine and glutamine formation and release were studied using the intact epitrochlaris preparation of rat skeletal muscle. Epinephrine reduced the release of alanine and glutamine in a concentration-dependent manner. Measurable inhibition was observed at 10(-9) M epinephrine, and maximal inhibition was obtained at 10(-5) M. Norepinephrine also reduced alanine and glutamine formation and release but the concentration required for maximal inhibition was approximately 100-fold greater than for epinephrine. Isoproterenol (beta agonist), but not phenylephrine (alpha agonist), reproduced the effects of epinephrine, and propranolol (beta antagonist), but not phentolamine (alpha antagonist), blocked the effect of the catecholamine. N6,O2'-Dibutyryl adenosine 3':5'-monophosphate reproduced the effects of epinephrine and theophylline potentiated the effect of submaximal concentrations of the hormone. Glucagon and prostaglandin E2 had no observable effect on amino acid release. Insulin did not modify the inhibition of alanine and glutamine release produced by epinephrine. Alanine and glutamine formation from added precursor amino acids was unaffected by epinephrine or cyclic adenosine 3':5'-monophosphate. Epinephrine reduced alanine formation in muscles obtained from diabetic rats or animals treated with thyroxine or cortisone. These findings indicate that physiological levels of catecholamines reduce alanine and glutamine formation and release from skeletal muscle. This effect is mediated by a beta-adrenergic receptor and the adenylate cyclase system and can be accounted for by an inhibition of muscle protein degradation.
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PMID:Alanine and glutamine synthesis and release from skeletal muscle. IV. beta-Adrenergic inhibition of amino acid release. 17 62

Amino acid deprivation and glucagon are both potent inducers of autography and proteolysis in liver. Because glucagon enhanced the metabolic utilization of some amino acids, the catabolic response to both of these stimuli could be achieved by a lowering of intracellular amino acid pools. Alternatively, glucagon could act independently of amino acids. To clarify the mode of hormonal action and also the relationship between the two cellular responses, livers from fed rats were perfused, with and without glucagon, with plasma amino acids over a concentration range of 0 to 10 times normal. Individual amino acids constancy at each level was ensured by perfusion in the single-pass mode. Amino acids alone strongly regulated autophagy and proteolysis in a coordinated fashion; maximal suppression was achieved at twice normal concentration; both effects increased rapidly to maximum at less than normal concentration. Corresponding effects of glucagon, however, could be elicited only at intermediate amino acid levels. None was noted at 4 and 10 times normal; at 0, hormonal stimulation was minimal. The amino acid inhibition was selective because it did not block cyclic AMP production or glycogenolysis. Intracellular pool measurements and systematic alteration of perfusate amino acid composition indicated that the autophagic and proteolytic effects of glucagon are mediated by a hormonally induced depletion of glycine, alanine, glutamate, and glutamine; of these, glutamine alone is the most effective. We conclude that the stimulation of intracellular protein degradation in liver is a manifestation of deprivation-induced autophagy which results from a decrease in certain intracellular glucogenic amino acids, notably glutamine.
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PMID:Glucagon-induced autophagy and proteolysis in rat liver: mediation by selective deprivation of intracellular amino acids. 29 Sep 94

Amino acids appear to be prime regulators of autophagy and proteolysis in liver. They both attain a maximum rapidly when livers from fed rats are perfused in the single-pass mode without amino acids and are suppressed to basal levels by amino acid additions. The fact that their greatest responsiveness to amino acids occurs slightly below normal plasma levels suggests that these cellular processes could play a role in regulating plasma amino acid concentrations in vivo. Autophagy and proteolysis are also inhibited by insulin and stimulated by glucagon. In the latter instance the hormonal action is not direct but mediated indirectly by depletion of intracellular glutamine, probably as a consequence of enhanced gluconeogenesis. Close correlations among (1) rates of intracellular proteolysis, (2) the aggregate volume of lysosomal elements, and (3) estimates of degradable protein internalized within lysosomes indicate that lysosomal function can explain total intracellular protein degradation (with the possible exception of rapidly turning over fractions) over the full range of proteolysis from maximum down to and including the basal state. Since ratios of degradable intralysosomal protein to corresponding rates of proteolysis in intact liver are constant over this range, protein internalization may be the rate-limiting step in lysosomal proteolysis.
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PMID:Application of liver perfusion as an in vitro model in studies of intracellular protein degradation. 39 92

Blood substrate and hormone concentration were determined in 16 children with Reye syndrome prior to and following administration of hypertonic glucose. Baseline concentrations of lactate, pyruvate, alanine, glutamine, glutamate, proline, hydroxyproline, lysine, and aspartate were elevated (p less than 0.01), whereas citrulline and arginine were low. All substrate concentrations were below or within the normal range following 36 hours of therapy except those of lactate, pyruvate, and aspartate. Urea nitrogen excretion was reduced (p less than 0.05) on the second day of therapy. Plasma concentrations of insulin and growth hormone increased and glucagon decreased during the first day. Cortisol remained elevated throughout the study period. We conclude that the high circulating concentrations of substrates are the result of both increased mobilization and decreased clearance and that hypertonic glucose infusion suppresses substrate mobilization. A primary abnormality of the mitochondria could explain the metabolic perturbations that occurred. A possible relationship between the encephalopathy in this disorder and an insult to both brain and brain capillary mitochondria is discussed.
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PMID:Metabolic response to hypertonic glucose administration in Reye syndrome. 66 61

1. Glucagon stimulated gluconeogenesis from glutamine in isolated liver cells to a far greater extent than that from any other amino-acid precursor. 2. Low concentrations of ammonium chloride (less than 1 mM) stimulated glucose production from glutamine. Glucagon further stimulated this glucose production, even in the presence of saturating concentrations of ammonium chloride. 3. In agreement with previous reports, glutamine hydrolysis by isolated mitochondria was found to be stimulated by ammonium chloride. It was found that ammonium chloride activated mitochondrial glutamine hydrolysis at the same concentrations at whict it stimulated glucose production from glutamine in liver cells. The effective activation of glutamine hydrolysis by ammonimum chloride in intact mitochondria was partially inhibited by rotenone and was abolished by uncoupling agents. 4. The addition of glucagon to hepatocytes metabolising glutamine led to a decrease in the intracellular concentration of glutamine and an increase in the intracellular concentration of glutamate. 5. It is likely that glucagon stimulates gluconeogenesis from glutamine by mechanisms which are additional to those that may operate in the stimulation of gluconeogenesis from other amino-acid precursors. It is suggested that both ammonium chloride and glucagon exert their effects on glutamine metabolism by increasing the effective activity of mitochondrial glutaminase (EC 3.5.1.2.).
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PMID:The effect of ammonium chloride and glucagon on the metabolism of glutamine in isolated liver cells from starved rats. 70 83


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