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

Glucagon treatment of rats allowed the isolation of liver mitochondria with enhanced rates of pyruvate metabolism measured in either sucrose or KCl media. No change in the activity of the pyruvate carrier itself was apparent, but under metabolizing conditions, use of the inhibitor of pyruvate transport, alpha-cyano-4-hydroxycinnamate, demonstrated that pyruvate transport limited the rate of pyruvate metabolism. The maximum rate of transport under metabolizing conditions was enhanced by glucagon treatment. Problems involved in measuring the transmembrane pH gradient under metabolizing conditions are discussed and a variety of techniques are used to estimate the matrix pH. From the distribution of methylamine, ammonia and D-lactate and the Ki for inhibition by alpha-cyano-4-hydroxycinnamate it is concluded that the matrix is more acid than the medium and that the pH of the matrix rises after glucagon treatment. The increase in matrix pH stimulates pyruvate transport. The membrane potential, ATP concentration and O2 uptake were also increased under metabolizing conditions in glucagon-treated mitochondria. These changes were correlated with a stimulation of the respiratory chain which can be observed in uncoupled mitochondria [Yamazaki (1975) J. Biol. Chem. 250, 7924--7930]. The mitochondrial Mg2+ content (mean +/- S.E.M.) was increased from 38.8 +/- 1.2 (n = 26) to 47.5 +/- 2.0 (n = 26) ng-atoms/mg by glucagon and the K+ content from 126.7 +/- 10.3 (n = 19) ng-atoms/mg. This may represent a change in membrane potential induced by glucagon in vivo. The physiological significance of these results in the control of gluconeogenesis is discussed.
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PMID:Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats. 2 27

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

In order to investigate the mechanisms of the hyperammonemia previously described in protein deprivation, the effects of sucrose and fasting on the ammonia metabolism were studied in control, streptozotocine-induced diabetics and colectomized rats. Hyperammonemia, hyperglutaminemia, hypouremia and intolerance to an ammonium load were observed in the control group after a 5 days sucrose-feeding. Any of these abnormalities were found in the diabetic animals whereas hyperglutaminemia did not occur in colectomized animals. It is concluded that protein deprivation obtained by sucrose feeding involves an hyperammonemia by a reduction of ureogenesis (which seemed to be related to an elevation of the ratio insulin/glucagon) and an hyperglutamininemia of colic origin.
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PMID:[Effect of protein deprivation on ammonia metabolism in the rat]. 15 10

When washed spleen slices from fed rats are incubated with 3 mm-[U-14C]glucose, the rate of glucose utilization (46.2 mumol/h per g dry wt.) is sufficient to account, theoretically, for 80% of the O2 consumption. Measurement of net lactate production, however, and the fate of the radioactive carbon, indicates that the contribution of glucose to the respiratory fuel of the tissue is only 25-30% whereas 60-70% of the glucose utilized is converted into lactate. At saturating glucose concentrations (above 5 mm) its contribution to the respiratory fuel of the slice is increased to a maximum value of 34-39%. Only 2% of the glucose utilized is metabolized via the oxidative steps of the pentose phosphate pathway. Starvation for 72 h marginally increases both the rate of glucose utilization (by 21%) and its net contribution to the respiratory fuel (by 29%). Insulin, glucagon, adrenaline and adenosine 3':5'-cyclic monophosphate have no significant effect on either the rate of glucose utilization or on the pattern of radioactive isotope distribution. The uptake of glucose is increased by only 20%, whereas the production of lactate doubles when slices are incubated under anaerobic conditions. In assessing the suitability of spleen slices for metabolic studies, the only serious major perturbation, compared with the freeze-clamped organ, is an elevated mitochondrial [NAD+]/[NADH] ratio (connected with increased endogenous NH3 production) that is partially restored to normal values on incubation with glucose. Equal proportions of erythrocytes and leucocytes are found in the washed spleen slice. Metabolic contributions of the constituent cell populations in the washed slice are calculated and it is concluded that lymphocytes account for the major part of the glycolytic metabolism (80-90%), whereas the contribution of erythrocytes is insignificant.
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PMID:Regulation of carbohydrate metabolism in lymphoid tissue. Quantitative aspects of [U-14C]glucose oxidation by rat spleen slices. 17 88

In an isolated rat liver perfusion system the effects of normothermal ischemia on hepatic functions were investigated. After 30 minutes of anoxy bile production and BSP elimination capacity of the liver are significantly reduced. The quantity of secreted "ascites" from the surface of the liver several times high after anoxic damage, while oxygen consumption, portal venous pressure and ammonia elimination do not differ significantly from the controls. Pretreatment with insulin plus glucose, isoproterenol, hypoxanthine, chlorpromazine and glucagon (5 micrograms/100 g i.v., or 0.2 mg/100 g s.c.) does not reduce noticeably the normothermal anoxic lesion of the liver Glucagon (50 micrograms/100 g i.v.), allopurinol, dibenzyline, ATP-MgCl2 and aspartic acid enhance significantly the ischemia-tolerance of liver in vitro.
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PMID:Ischemic damage of the liver. Part I: In vitro investigation of the prevention of the ischemic lesion of the liver. 49 24

The effect on free plasma amino acids before and after infusion of 1 mg glucagon was studied at rest after an overnight fast in seven patients with compensated liver cirrhosis and in seven healthy controls. Total aminoacidaemia in cirrhotic patients is significantly higher than in controls. Elevated basal levels in cirrhotics are found particularly in tyrosine, citrulline, tryptophane, threonine, phenylalanine, and methionine whereas ornithine and serine levels are decreased. Save for the redox couple cystine-cysteine which increases, glucagon elicits an decrease in most amino acids that is proportionate to their initial level. Total aminoacidaemia decreases in controls and cirrhotics by 14.6 and 9.1 per cent respectively. Serum ammonia level rises significantly in both groups, urea increases only in controls, uricaemia remains virtually unchanged.
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PMID:The effect of glucagon on free plasma amino acids in cirrhotics and healthy controls. 63 37

The phenomenon of natriuresis during the early phase of total starvation has been described in man and rabbit. We have examined the pattern of electrolyte excretion initiated by starvation for 4 days in the male Wistar rat. Within 24 hr sodium excretion is significantly diminished when compared to prestarvation values (control 2.55 +/- 0.76 [S.D.] mEq/day; 1-day fast 0.42 +/- 0.27) and by day 2 is less than one tenth of the control value. Chloride retention parallels this sodium conservation. Concomitant changes in urinary pH and ammonia excretion (UNH4V) reflect the mild acidosis of starvation (control pH 7.46 +/- 0.18 [S.D.], UNH4V 0.21 +/- 0.08 [S.D.] mEq/day; day 2 pH 6.10 +/- 0.31, UNH4V 0.71 +/- 0.21). However, the excretion of organic acids is not elevated but is actually decreased by day 2 (control 1.02 +/- 0.21 [S.D.] mEq/day; day 2 0.66 +/- 0.26). The majority of the organic acids are excreted as salts (day-2 0.51 +/- 0.21). This level of excretion does not obligate excessive sodium loss and can be adequately matched by renal ammonia production. Normal plasma glucose levels are maintained, consistent with the well-documented increase in renal gluconeogenesis in the starved rat. Plasma levels of glucagon, a known natriuretic and ketogenic agent, do not rise, and this together with a normal plasma glucose concentration may account for the failure of the rat to exhibit the natriuresis of starvation that is observed in man and rabbit.
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PMID:Renal sodium conservation during starvation in the rat. 64 88

Adenylosuccinase activity of rat liver is depressed by prolonged starvation, cortisol administration, high protein diets, and alloxan diabetes. The loss of activity is not due to the accumulation of a dissociable inhibitor or loss of a cofactor. Starvation produces no loss in activity for 1 day; thereafter the activities of the liver and spleen enzyme decay with a half-life of about 0.9 day. Starvation produces no change in the activity of the kidney, brain, and skeletal muscle enzyme. Refeeding restores the activity of the liver enzyme to the fed level, with only a slight overshoot. The recovery of adenylosuccinase activity is equally rapid after refeeding a balanced diet, or corn oil, or glucose, and is not inhibited by injection of glucagon, in contrast to malic enzyme activity. Recovery is inhibited by cycloheximide, indicating the involvement of protein synthesis. Althouth adenylosuccinase is depressed in liver of starving rat it is elevated in liver of starving chicken. Starvation depresses malic enzyme activity and elevates alanine aminotransferase activity in both species. When rats are starved, the rate of de novo synthesis of adenine mononucleotide decreases in spleen and liver but not in kidney, suggesting a regulatory role for adenylosuccinase in purine biosynthesis. The low activity of adenylosuccinase in liver of severely starved rats is inconsistent with the proposal (Moss, K. M., and McGivan, J.D. (1975) Biochem. J. 150, 275-283) that the purine nucleotide cycle plays a major role in ammonia production for urea synthesis, at least under these conditions.
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PMID:Effect of diet on adenylosuccinase activity in various organs of rat and chicken. 69 Jan 30

Previous findings that 2.5 mM quinolinic acid inhibits gluconeogenesis more strongly from alanine than from lactate have been confirmed. 15 mM quinolinic acid completely inhibited gluconeogenesis from lactate as well as from alanine whereas the formation of glucose from fructose and the production of urea from ammonia and lactose were not affected. The pattern of the gluconeogenic intermediates was the same in the presence of 15 mM quinolinic acid as with 2.5 mM of the inhibitor. It is concluded that high as well as low concentrations of quinolinic acid inhibit gluconeogenesis at the step between oxaloacetate and phosphoenolpyruvate. Furthermore, 5-methoxyindole-2-carboxylic acid, an inhibitor of mitochondrial pyruvate metabolism, also completely blocked gluconeogenesis from lactate whereas glycerol conversion to glucose was only weakly inhibited. All these results do not support the concept of an alternate pathway of gluconeogenesis from lactate proposed by others. 2.5 mM quinolinic acid also partially blocked the formation of urea from alanine. It is suggested that quinolinic acid may have a second site of action causing an inhibition of the glutamate-pyruvate transamination owing to lack of 2-oxoglutarate in the cytosol. In the presence of quinolinic acid, glucagon caused about the same increase in aspartate and malate tissue levels in the absence of added substrates as in the presence of added lactate or alanine. Therefore, no additional effect of glucagon on gluconeogenesis from lactate or alanine prior to the block by quinolinic acid could be demonstrated.
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PMID:Effects of quinolinic acid and glucagon on gluconeogenesis in the perfused rat liver. 69 6

The glucagon-secreting potency of 22 amino acids was investigated in the rat isolated perfused pancreas. Arginine and the structurally related amino acids were the most potent A2-cell stimulators that induced a biphasic and sustained glucagon release. Dose-response curver were different for L(+) and D(+)arginine, and the suppressor effect of glucose on the response to L(+) arginine was not detected in the presence of D(+) arginine or homoarginine. Citrulline was the only exception among the arginine-related amino acids; it displayed neither stimulatory nor inhibitory potency on glucagon release. The A2-cell response to D(+) amino acids and artificial analogues of arginine is a strong case for the theory of amino acid receptors' triggering the release of the hormone before (or in the absence of) further metabolism. The prominent rank of arginine and ornithine amont stimulatory amino acids and some other physiologic evidence suggest that A2-cell may play a regulatory role in the metabolsm of ammonia by the liver.
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PMID:Glucagon secretion induced by natural and artificial amino acids in the perfused rat pancreas. 84 11


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