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)

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.
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PMID:ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I. 27 29

Chloralose-anaesthesized dogs, starved for 24 hours, were used to determine the effects of 10 microgram/kg glucagon, administered i.v. as a single bolus injection, on liver substrates in situ (glycogen, glucose-1-phosphate, glucose-6-phosphate, glucose, fructose-6-phosphate, fructose-1,6-diphosphate, triose phosphates, glycerol-3-phosphate, phosphoenolypyruvate, pyruvate, lactate, citrate, malate, ATP, ADP, and AMP). liver samples were obtained by instant deep-freezing with Wollenberger clamps on four consecutive occasions at 10-minute intervals. Heart rate and blood pressure were continuously monitored. Serial liver sampling per se had no significant effects on liver metabolism or systemic haemodynamics in a group of control animals. In a second group glucagon, administered after the initial freeze-clamp sampling to obtain baseline values, led to a marked activation of the glycogenolytic pathway resulting in glucose release from the liver.
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PMID:Effects of glucagon on liver metabolism in intact dogs. 92 72

Glucagon effectively prevented the increase in glucose-6-phosphate dehodrogenase activity of rat liver following the administration of a glucose-casein mixture without altering the amount of the diet consumed. However, the increase of the enzyme level in carbon tetrachloride-injured rat liver was virtually insensitive to glucagon. The results obtained gave further evidence for the difference between these two induction mechanisms of glucose-6-phosphate dehydrogenase.
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PMID:Differential effects of glucagon on induction of rat liver glucose-6-phosphate dehydrogenase by liver injury and dietary change. 127 34

Excessive amounts of glucose enter the systemic circulation when patients with non-insulin-dependent diabetes mellitus (NIDDM) eat a carbohydrate-containing meal. To determine the contribution of hepatic glucose cycling (defined as the net effect of glucose/glucose-6-phosphate cycling and uptake and release of glucose from hepatic glycogen) to postprandial hyperglycemia, diabetic, glucose-intolerant, and nondiabetic subjects were fed mixed meals. The meal contained both [2-3H]glucose (an isotope that is extensively detritiated during hepatic glucose cycling) and [6-3H]glucose (an isotope that is not detritiated during hepatic glucose cycling). Of the 50 g of carbohydrate contained in the meal, approximately 4-8 g underwent hepatic glucose cycling. Although total cycling of ingested glucose did not differ between diabetic, glucose-intolerant, and nondiabetic subjects (361 +/- 67 vs. 494 +/- 106 vs. 322 +/- 44 mumol.kg-1.5 h-1, respectively), the data suggested that hepatic cycling was increased in the diabetic and glucose-intolerant individuals but not in the nondiabetic subjects during the first 2 h after eating. Hepatic cycling during the first 2 h after eating was correlated with the prevailing glucagon concentration (r = 0.6, P less than 0.01) and increased (P less than 0.05) as hepatic glucose release increased. Hepatic glucose cycling had a marked effect on the measurement of so-called initial splanchnic glucose uptake. Nevertheless, however measured, initial splanchnic glucose uptake was not decreased and, if anything, was increased in diabetic and glucose-intolerant patients. Integrated postprandial hepatic glucose release increased (r less than 0.01) with the severity of fasting hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution to postprandial hyperglycemia and effect on initial splanchnic glucose clearance of hepatic glucose cycling in glucose-intolerant or NIDDM patients. 201 76

Development of hypoglycemia, a slight decrease in concentration of glucagon in blood as well as increase in activity of malate-and glucose-6-phosphate dehydrogenases in liver cytosol were detected in rats injected subcutaneously with nicotinamide at a dose of 31.25 mg/kg 6 hrs before decapitation. Increase of the single dose up to 125 mg/kg caused hypoglycemia, distinct increase in concentration of insulin and glucagon in blood plasma simultaneously with a pronounced inhibition of the enzymatic activity in liver tissue. Effect of nicotinamide on carbohydrate metabolism appears to have a dissimilar character depending on the drug dose: its small doses accelerated utilization and oxidation of glucose but did not affect the secretion of insulin and glucagon.
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PMID:[Change in carbohydrate metabolism, secretion of insulin and glucagon in normoglycemic rats during administration of various doses of nicotinamide]. 252 38

(1) The rate of palmitate oxidation in the 7800 C1 Morris hepatoma cells was about 60% of the activity observed in hepatocytes. The stimulatory effect of glucagon in hepatocytes was not observed in the hepatoma cells. The rate of fatty acid synthesis from [2-14C]acetate in the hepatoma cells was 1/20 of the activity in hepatocytes. The conversion of [2-14C]acetate to cholesterol was not different in the two kinds of cell. (2) Acetyl-CoA carboxylase and fatty acid synthetase were significantly decreased in the hepatoma cells. The hepatoma cells had, however, raised activities of malate dehydrogenase (decarboxylating), and glucose-6-phosphate and 6-phosphogluconate dehydrogenases. (3) The activities of the enzymes were not affected by different concentrations of glucose or palmitate in the culture medium. Insulin, dexamethasone, triiothyronine and glucagon had no effect on the enzyme activities. This is in contrast to the adaptation of the peroxisomal beta-oxidation system, which is induced by fatty acids and modified by hormones.
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PMID:Activities of enzymes of lipid metabolism in Morris hepatoma 7800 C1 cells. 256 35

The role of endogenous glucagon and insulin on the hepatic glycogen and triglyceride storage syndrome in propylthiouracil (PTU)-induced hypothyroidism was investigated in the chick. PTU feeding in the diet resulted in a progressive increase in liver glycogen concentration associated with a concomitant decrease in hepatic glucose-6-phosphatase (G-6-Pase) activity. Plasma glucagon level was significantly decreased and insulin significantly increased after two days of PTU administration. These enzyme and hormone changes were associated with a significant increase in hepatic glucose-6-phosphate (G-6-P) and a decrease in cyclic AMP levels. Although our results do not directly prove, the data does suggest that the hepatic glycogen storage syndrome observed in the PTU-induced hypothyroidism in the chick is mediated through changes in pancreatic glucagon and insulin secretion. The extent of glycogen accumulation was inversely related to G-6-Pase which is a rate limiting glycogenolytic enzyme. A significant increase in the plasma insulin/glucagon ratio, along with a significant decrease in the hepatic cyclic AMP concentration, could most likely also account for the excessive hepatic triglyceride accumulation in the PTU-treated chicks.
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PMID:Elevated insulin/glucagon ratios and decreased cyclic AMP levels accompany the glycogen and triglyceride storage syndrome in the hypothyroid chick. 624 95

The quantity of translatable mRNA of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) in primary cultures of adult rat hepatocytes subjected to different hormonal conditions was determined with a reticulocyte-lysate, cell-free system. The level of glucose-6-phosphate dehydrogenase mRNA was about 5-fold higher in the presence of insulin than in its absence. This increase of glucose-6-phosphate dehydrogenase mRNA reached a maximum 12 h after the addition of insulin. The maximum level of induction of glucose-6-phosphate dehydrogenase mRNA required 10(-8) M insulin. Glucagon and triiodothyronine had no effect on the glucose-6-phosphate dehydrogenase mRNA level. The increase of glucose-6-phosphate dehydrogenase activity correlated with the increase in level of mRNA of this enzyme. This suggests that the changes in glucose-6-phosphate dehydrogenase activity in response to the above hormonal changes are primarily due to changes in the amount of mRNA coding for this enzyme.
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PMID:Hormonal regulation of translatable mRNA of glucose-6-phosphate dehydrogenase in primary cultures of adult rat hepatocytes. 635 22

The plasma levels of corticosterone, insulin and glucagon, and the concomitant changes in the levels of several liver enzymes and metabolites were measured in intact rats in the basal state during 24 hours and under conditions of food deprivation and hypoxia. The levels of the following enzymes and metabolites were examined: phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, pyruvate kinase, phosphofructokinase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, glucose, glucose-6-phosphate, glycogen, fructose-6-phosphate, hexokinase, tyrosine amino-transferase and tryptophan oxygenase. During food deprivation, the increased gluconeogenesis is possibly a result of glucagon activity. In contrast, however, during hypoxia the increase in gluconeogenesis seems to be a result of the higher plasma level of corticosterone. During starvation, the insulin concentration dropped steadily and came close to zero.
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PMID:Plasma concentrations of glucose, corticosterone, glucagon and insulin and liver content of metabolic substrates and enzymes during starvation and additional hypoxia in the rat. 703 Aug 99

In a previous study, administration of casein hydrolysate to food-deprived rats at a dose of 4 g/kg body wt resulted in an increase in portal plasma glucagon concentration. This was associated with an activation of phosphorylase a and a decrease in hepatic glycogen concentration. The present study was undertaken to determine whether similar results would be obtained with smaller doses. Doses of 1 and 2 g/kg body wt were administered to food-deprived rats. At a dose of 2 g/kg, portal plasma glucagon concentration was significantly elevated. This was associated with a slight increase in phosphorylase a activity (P < 0.05) and a 50% decrease in hepatic glycogen concentration (P < 0.01). At a dose of 1 g casein hydrolysate/kg body wt, changes in portal plasma glucagon concentration, phosphorylase a activity and hepatic glycogen concentration generally were not observed. Hepatic glucose, uridine diphosphoglucose, ATP and glucose-6-phosphate concentrations were unaffected by either dose of casein hydrolysate. The data indicate a dose-response relationship between casein hydrolysate administration and effects on glycogen metabolism in the liver. Protein-induced glycogenolysis is likely to occur when rats ingest a moderate amount of a pure protein meal.
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PMID:Physiological doses of oral casein affect hepatic glycogen metabolism in normal food-deprived rats. 773 75


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