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)

Genetically obese normotensive rats, LA/N-corpulent (cp), were fed ad libitum diets containing either 54% sucrose or cooked corn starch for 12 weeks. Twenty-four rats were used for the study; half were corpulent (cp/cp) and half were lean (cp/+ or +/+). Fasting levels of plasma insulin, glucose, corticosterone, glucagon and growth hormone, and activities of liver and epididymal fat pad glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), and liver and kidney glucose-6-phosphatase (G6Pase), fructose 1,6-diphosphatase (FDPase), and phosphoenolpyruvate carboxykinase (PEPCK) were measured. A significant phenotype effect was observed in insulin, corticosterone, growth hormone, and liver G6PD, ME, FDPase, and kidney PEPCK, G6Pase, FDPase, and epididymal fat pad G6PD and ME (corpulent greater than lean), and glucagon (lean greater than corpulent). Diet effect (sucrose greater than starch) was significant for plasma glucose, liver ME, and kidney G6Pase. Although not significant at the P less than 0.05 level, insulin, corticosterone, liver G6PD and FDPase and kidney FDPase tended to be higher in sucrose-fed rats. This study suggests that the corpulent rat is more lipogenic and gluconeogenic than the lean, and that the hormones responsible are effective in keeping both the lipogenic and gluconeogenic enzyme activity elevated.
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PMID:Hormonal and lipogenic and gluconeogenic enzymatic responses in LA/N-corpulent rats. 399 2

The continuous infusion of a low dose of glucagon (35 micrograms/kg/d, for 5 d) constitutes, in view of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities, a reliable experimental model of hyperglucagonemia. By conjunction of monooxygenase assays and immunoquantitation of specific isozymes of cytochrome P-450, the actual inducing ability of glucagon has been shown and it might explain some of the modifications of the drug metabolizing system in diabetic mice. The isozymic pattern of cytochrome P-450 of liver microsomes from diabetic mice appears very different from that produced by classical inducers.
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PMID:The effect of different hyperglucagonemic states on monooxygenase activities and isozymic pattern of cytochrome P-450 in mouse. 402 53

Primary cultures of adult rat hepatocytes were kept for 46 h with either insulin ('insulin cells') or glucagon ('glucagon cells') as the dominant hormone under different oxygen concentrations with 13% (v/v) O2 mimicking arterial and 4% hepatovenous levels. Thereafter metabolic rates were measured for a 2 h period under the same ('overall long-term O2 effects') or a different ('short-term O2 effects') oxygen concentration. From the differences of the two effects the 'intrinsic long-term O2 effects' were derived. Glycolysis, as measured in 'insulin-cells', was stimulated by low O2 levels. It was about threefold faster in cells cultured and tested under 4% O2 as compared to cells cultured and tested under 13% O2, indicating the overall long-term effect. Glycolysis was about twofold faster in cells cultured and tested under 4% O2 as compared to cells cultured under 4% O2 but tested under 13% O2, demonstrating the short-term effect. Glycolysis was about 1.5-fold faster in cells cultured and tested under 4% O2 as compared to cells cultured under 13% O2 but tested under 4% O2, showing the intrinsic long-term effect. This difference was roughly parallel to the difference in levels of glucokinase and pyruvate kinase. Gluconeogenesis, as measured in 'glucagon cells', was stimulated by high O2 levels. Similar to glycolysis overall long-term, short-term and intrinsic long-term effects could be distinguished. The intrinsic long-term effects determined under 13% O2 corresponded to a 1.5-fold stimulation and paralleled the difference in phosphoenolpyruvate carboxykinase levels. The present results show that physiological oxygen concentrations also modulate hepatic carbohydrate metabolism by long-term effects and that the O2 gradient over the liver parenchyma thus contributes to the metabolic differences between periportal and perivenous hepatocytes in vivo.
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PMID:Long-term effects of physiological oxygen concentrations on glycolysis and gluconeogenesis in hepatocyte cultures. 402 36

By using very low concentrations of cells to minimize alterations in substrate concentrations, we demonstrated that the lactate/pyruvate ratio of the incubation medium, which determines the cytosolic NADH/NAD+ ratio, affects gluconeogenic flux in suspensions of isolated hepatocytes from fasted rats. At a fixed extracellular pyruvate concentration of 1 mM and with the lactate/pyruvate ratio varied from 0.6 to 10 and to 50, glucose production rates increased from 2.5 to 5.5 and then decreased to 1.8 nmol/mg of cell protein/min. This finding paralleled the observation of Sugano et al. (Sugano, T., Shiota, M., Tanaka, T., Miyamae, Y., Shimada, M., and Oshino, N. (1980) J. Biochem. (Tokyo) 87, 153-166) who noted a similar biphasic response in the perfused liver system when lactate was held constant and pyruvate varied. The biphasic relationship can be explained by the influence of the NADH/NAD+ ratio on the near-equilibrium reactions catalyzed by glyceraldehyde-3-phosphate dehydrogenase and malate dehydrogenase in the hepatocyte cytosol. By shifting the equilibrium of the glyceraldehyde-3-phosphate dehydrogenase reaction, a rise in the NADH/NAD+ ratio decreases the concentration of 3-phosphoglycerate which, because of the linkage of 3-phosphoglycerate to phosphoenolpyruvate through two near-equilibrium reactions, reduces the concentration of phosphoenolpyruvate and therefore causes a decline in flux through pyruvate kinase. This decrease in pyruvate kinase flux results in an enhanced gluconeogenic flux. At higher NADH/NAD+ ratios, however, the oxalacetate concentration drops to such an extent that the consequent decreased flux through phosphoenolpyruvate carboxykinase exceeds the decline in flux through pyruvate kinase, producing a decrease in gluconeogenic flux. The lactate/pyruvate ratio was found to influence the actions of three hormones thought to stimulate gluconeogenesis by different mechanisms. Except for an inhibition by glucagon seen at the lowest lactate/pyruvate ratio tested, the stimulations by this hormone were relatively insensitive to lactate/pyruvate ratios, while angiotensin II produced greater stimulations of gluconeogenesis as the lactate/pyruvate ratio was increased. Dexamethasone, added in vitro, stimulated gluconeogenesis significantly only at very low and very high lactate/pyruvate ratios.
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PMID:The interaction between the cytosolic pyridine nucleotide redox potential and gluconeogenesis from lactate/pyruvate in isolated rat hepatocytes. Implications for investigations of hormone action. 404 7

Hepatocytes, isolated from fasted rats, were incubated with graded concentrations of lactate and pyruvate, at a mean constant ratio of 10-13:1, to alter systematically the concentrations of gluconeogenic intermediate metabolites and rates of glucose production. By analyzing glucose production rates as a function of corresponding concentrations of extracellular pyruvate, cytosolic oxalacetate, and cellular 3-phosphoglycerate in the presence and absence of hormones and assuming no primary activation of phosphoenolpyruvate carboxykinase, estimates were made of the relative contributions of stimulation of formation of cytosolic oxalacetate and inhibition of pyruvate kinase to hormonal stimulations of gluconeogenesis. Addition of dexamethasone, glucagon, or angiotensin II did not cause a shift in the relationship between cellular 3-phosphoglycerate concentrations and rates of glucose production, indicating that there was no effect of these agents on the reactions involved in conversion of phosphoenolpyruvate to glucose. All three agents shifted the relationships between rates of glucose production and both cytosolic oxalacetate and extracellular pyruvate. The following conclusions were drawn from computer analyses of these results. At low concentrations of pyruvate, stimulation of oxalacetate production and pyruvate kinase inhibition were approximately equally contributory to the overall stimulations of gluconeogenesis by angiotensin II and dexamethasone. At higher pyruvate concentrations, pyruvate kinase inhibition by angiotensin II played a greater role, accounting for 90% of the overall stimulation. For dexamethasone, as the pyruvate concentration was increased, stimulation of gluconeogenesis resulting from enhanced formation of oxalacetate diminished as did overall stimulation of gluconeogenesis. Glucagon addition resulted in an inhibition of pyruvate kinase flux that accounted for 75% of the hormone's overall effect at low pyruvate concentrations; this increased to 95% at high pyruvate concentrations.
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PMID:Estimation of the relative contributions of enhanced production of oxalacetate and inhibition of pyruvate kinase to acute hormonal stimulation of gluconeogenesis in rat hepatocytes. An analysis of the effects of glucagon, angiotensin II, and dexamethasone on gluconeogenic flux from lactate/pyruvate. 404 8

The hyperglycemic response of adult male Wistar rats given dieldrin (63 mg/kg, po) and either phenobarbital (40 mg/kg, ip), atropine (4 mg/kg, sc), L-alpha-methyldopa (200 mg/kg, ip), or DL-propranolol (8 mg/kg, sc) was studied. The hyperglycemia was maximal (73% above control values) 2 hr after exposure to dieldrin alone. Phenobarbital reduced the hyperglycemia by 41% and abolished dieldrin-induced convulsions. It also prevented the increases that dieldrin causes in hepatic phosphoenolpyruvate carboxykinase (PEPCK) activity. These results suggest that the dieldrin-induced hyperglycemia is mediated via the CNS. Atropine prevented the hyperglycemia for 2 hr and delayed the attainment of maximal glucose concentrations for another 2 hr. However, additional atropine 4, 8, 12, and 18 hr after the dieldrin had no effect. Atropine also increased (125%) the time to the onset of dieldrin-induced convulsions. It did not alter hepatic PEPCK activity. L-alpha-Methyldopa decreased (24%) the hyperglycemic response in the first 2 hr after dieldrin treatment. It caused similar reductions in blood glucose when given during the peak hyperglycemic response. L-alpha-Methyldopa also reduced (49%) the dieldrin-effected increase in hepatic PEPCK activity. DL-Propranolol did not alter the effects of dieldrin. Thus these data suggest that the dieldrin-induced hyperglycemia is mediated by the CNS, primarily via enhanced cholinergic activity and secondarily by increased alpha-adrenergic activity. It is suggested that the pancreas responds to the cholinergic outflow by increasing the secretion of glucagon while simultaneously responding to the alpha-adrenergic outflow by decreasing insulin secretion.
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PMID:The effects of phenobarbital, atropine, L-alpha-methyldopa, and DL-propranolol on dieldrin-induced hyperglycemia in the adult rat. 404 84

1. The effect of Ca(2+), glucagon, adrenaline and adenosine 3':5'-cyclic monophosphate on gluconeogenesis by rat kidney-cortex slices was studied. 2. Glucose formation from a range of substrates, with the exception of glycerol, was increased by an increase in extracellular Ca(2+) concentration. 3. Hormones and adenosine 3':5'-cyclic monophosphate, at low Ca(2+) concentrations, stimulated glucose production from several substrates, but not from glycerol, fructose, malate or fumarate. 4. Hormonal stimulation was not detected in the absence of Ca(2+) or at 2.5mm-Ca(2+). 5. Ca(2+), hormones and adenosine 3':5'-cyclic monophosphate had no effect on phosphoenolpyruvate carboxylase activity. 6. It is proposed that Ca(2+) and adenosine 3':5'-cyclic monophosphate-mediated hormone action activate the same rate-limiting step in gluconeogenesis: this step is tentatively identified as the rate of transfer of substrates across the mitochondrial membrane.
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PMID:Regulation of renal gluconeogenesis by calcium ions, hormones and adenosine 3':5'-cyclic monophosphate. 435 84

The metabolic response to the first fast experienced by all mammals has been studied in the newborn rat. Levels of fuels and hormones have been compared in the fetal and maternal circulations at term. Then, after cesarean section just before the normal time of birth, sequential changes in the same parameters were quantified during the first 16 h of the neonatal period. No caloric intake was permitted, and the newborns were maintained at 37 degrees C. Activities of three key hepatic enzymes involved in glucose production were estimated. Marked differences in maternal and fetal hormones and fuels were observed. Lower levels of glucose, free fatty acids, and glycerol but higher levels of lactate, alpha-amino nitrogen, alanine, and glutamine were present in the fetus. Pyruvate, glutamate, and ketone bodies were not significantly different. The combination of a strikingly higher fetal immunoreactive insulin and a slightly lower immunoreactive glucagon (pancreatic) resulted in a profound elevation in the insulin-to-glucagon ratio, a finding consistent with an organism in an anabolic state. The rat at birth presents a body composition with respect to fuels available for mobilization and conversion which is dominated by carbohydrate and protein, since little fat is present. However, at birth a transient period of hypoglycemia occurred, associated with a rapid fall in insulin and rise in glucagon, causing reversal of the insulin-to-glucagon relationship toward ratios such as were observed in the mother. After a lag period, hepatic activities of phosphorylase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase increased. Concurrent with these enzyme changes, the blood glucose returned to levels at or above those of the fetus. Interestingly, the fall observed in levels of the gluconeogenic precursors, lactate and amino acids, preceded the rise in enzyme activities and restoration of blood glucose. After 4 h, however, hypoglycemia recurred, during a period of decreasing hepatic glycogen content and blood lactate, pyruvate, and glycerol levels but of stable or increasing amino acid concentrations. Hepatic gluconeogenesis in this phase of depleted glycogen stores was insufficient to maintain euglycemia. Substrates derived from fat showed early changes of smaller magnitude. The rise in free fatty acids which occurred was less than twofold the value at birth, though this rise persisted up to 6 h. Whereas glycerol rose transiently, acetoacetate did not change and beta-hydroxybutyrate concentration fell. Both ketone bodies showed a marked rise at 16 h. at a time of diminished free fatty acid levels. Plasma growth hormone, though higher in the fetal than the maternal circulation, showed no consistent change during the period of observation. The changes in levels of the endocrine pancreatic hormones at birth were appropriate in time, magnitude, and direction to be implicated as prime regulators of the metabolic response during the neonatal period in the rat.
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PMID:Fuels, hormones, and liver metabolism at term and during the early postnatal period in the rat. 475 Apr 49

1. Administration of glucagon to foetal rats produced a 10-15-fold increase in hepatic phosphoenolpyruvate carboxykinase activity together with a similar increase in the overall pathway of pyruvate conversion into glycogen in liver slices. 2. Glucagon was without effect on gluconeogenesis in vivo, which remained at approx. 0.1% of the incorporation as measured in newborn animals. 3. The apparent discrepancy between these results was due to the ether anaesthesia that was required for experimentation in vivo. Under conditions when minimal ether was used, the rates of labelling of glycogen from [3-(14)C]pyruvate in vivo were increased 10-20-fold and there was an additional stimulus by glucagon. 4. Ether anaesthesia produced a more reduced redox state of the foetal liver cytosol and lowered the ATP/ADP concentration ratio. 5. It is proposed that these effects are significant in the limitation of gluconeogenesis in the foetal rat liver, so that only with high phosphoenolpyruvate carboxykinase activity, high ATP concentration and a relatively oxidized cytosol redox state will a functional gluconeogenic pathway be present.
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PMID:The development of gluconeogenesis in rat liver. Effects of glucagon and ether. 549 60

Key enzymes of gluconeogenesis in the liver, phosphoenolpyruvate carboxykinase [EC 4.1.1.32] and glucose-6-phosphatase [EC 3.1.3.9], were studied in patients with primary or metastatic hepatic cancer. Liver specimens for enzyme assay were obtained by necropsy performed within four hours after death. It was confirmed that both enzyme activities in rat liver preserved at 4 degrees C remained unchanged within nine hours after the removal of the tissue. Activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase decreased to below ten per cent of the control in neoplastic liver tissue of patients with hepatocellular carcinoma accompanied with liver cirrhosis. These two enzyme activities in cirrhotic tissue of patients with hepatocellular carcinoma were lower than those in patients merely with cirrhosis. In patients with metastatic hepatic cancer both two enzyme activities further decreased and were scarcely detected not only in neoplastic tissue but also in non-neoplastic tissue. These results show that hepatic gluconeogenesis markedly decreases in patients with primary or metastatic hepatic cancer. The biochemical analysis of the blood in hepatic cancer, decreased in blood glucose and release in immunoreactive glucagon, also suggested the suppression of gluconeogenesis.
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PMID:Hepatic gluconeogenic key enzymes in patients with hepatic cancer. 625 51


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