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)

After the infusion of fructose, 0.25 g/kg body weight, blood uric acid levels were significantly increased above the mean basal value in five patients with glycogen storage disease (GSD), type I (P less than 0.02-P less than 0.05). The mean fasting blood inorganic phosphate (Pi) level in the patients was 3.9 +/- 0.3 mg/100 ml and was significantly lower than the mean Pi value of 4.8 +/- 0.3 mg/100 ml of the control subjects (P less than 0.05). Blood Pi levels were significantly lower in the patients than in the control subjects at varying times after the administration of fructose (P less than 0.005-P less than 0.05). Uric acid excretion did not increase significantly in the patients after fructose was given. In contrast to normal children, the mean peak blood uric level in the patients increased significantly after the administration of glucagon (P less than 0.001). In both patients (P less than 0.005) and control subjects (P less than 0.05), mean blood Pi concentrations decreased significantly after the administration of glucagon; however, the blood Pi concentrations in the patients were significantly lower than in the control subjects. Uric acid excretion increased after glucagon administration in both patients and control subjects, but the differences in uric acid excretion between the two groups were not significant. The data in our patients after fructose and glucagon administration suggest that hyperuricemia in GSD results from enhanced nucleotide catabolism. The concentrations of hepatic Pi and ATP may be low in patients with GSD; hepatic Pi and ATP content would therefore be further diminished by the administration of fructose and glucagon. By a mechanism similar to that of fructose-induced hyperuricemia, diminished hepatic Pi and ATP content might increase the breakdown of adenine nucleotides with resultant hyperuricemia.
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PMID:The pathogenesis of hyperuricemia in glycogen storage disease, type I. 26 62

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

Recent experiments have demonstrated that stimulation of rat hepatocyte alpha-adrenergic receptors alters the activity of enzymes known to be regulated by cycles of phosphorylation and dephosphorylation. These events apparently occur without an increase in the activity of adenosine 3':5'-monophosphate-dependent protein kinase. The present study compared the effects of glucagon and catecholamines on the incorporation of radioactive phosphate into cytosolic proteins obtained from intact rat hepatocytes. Sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis resolved 27 phosphorylated bands in the molecular weight range 220,000 to 29,000. Treatment of the intact hepatocytes with glucagon or cyclic nucleotides increased the phosphorylation of 12 of these bands. Incubation of unlabeled cytoplasmic proteins with the catalytic subunit of protein kinase and [gamma-32P]ATP leads to the phosphorylation of 11 proteins. The molecular weights of these proteins were very similar to those altered by glucagon treatment of intact cells. Stimulation of the alpha-receptor with norepinephrine, epinephrine, or phenylephrine in the presence of 20 micrometer propranolol caused an increase in the phosphorylation of at least 10 of the same 12 phosphorylated bands stimulated by glucagon. The increase in phosphorylation mediated by alpha-receptors was only 50 to 60% of that observed with glucagon and occurred in the absence of any change in the level of adenosone 3':5'-monophosphate. The effects of alpha-receptor stimulation could be completely antagonized by 20 micrometer ergotamine or 20 micrometer phentolamine. Treatment of the cells with the Ca2+ ionophore A23187 in an attempt to mimic alpha-receptor function increased the phosphorylation of 4 of the phosphoproteins altered by glucagon or catecholamines. The effects of the ionophore depended on the presence of extracellular Ca2+ ion and were similar in magnitude to those of catecholamines. It is concluded that alpha-receptor occupation alters the activity of an adenosin 3':5'-monophosphate-independent protein kinase or phosphatase with a specificity similar to those affected by cyclic nucleotides.
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PMID:The effects of glucagon, catecholamines, and the calcium ionophore A23187 on the phosphorylation of rat hepatocyte cytosolic proteins. 35 36

The irreversible reaction between liver esterases and the active-site-directed inhibitor bis(4-nitrophenyl)phosphate can be used in vivo both for the estimation of the esterase contents and for the measurement of the esterase degradation rates. A method based on this reaction is described which allows the simultaneous estimation of the rate constants of degradation and synthesis of esterases during a period of change in protein concentration. Rat liver was found to contain about 1 mg of organophosphate-binding esterases per g of fresh tissue while the microsomal fraction contains about 30 mg of esterases per g of microsomal protein. Esterase degradation and de novo synthesis were shown to remain in equilibrium for a period of at least five days following the injection of 10 mg bis(4-nitro-[14C]phenyl)phosphate per kg. The decrease of the relative amount of labeled esterases with time was found to follow first-order kinetics yielding an average esterase degrading constant of 0.0165 h-1 which corresponds to a half-life of 42 h. These data were confirmed by an independent experiment using one of the standard procedures for the estimation of degradation rates: [14C]leucine was incorporated and one of the esterases was subsequently isolated by immuno-precipitation. Using isoelectric focussing and dodecyl sulfate electrophoretic methods, the various esterase isoenzymes appeared to have very similar, if not identical turnover rates. This method for the estimation of the turnover characteristics was applied to evaluate hormone effects on liver esterases. The time course of the contents and the turnover of liver esterases was measured under the influence of glucagon treatment in diabetic rats and under the influence of high doses of insulin. The esterase content decreased faster than the average content of microsomal protein under the influence of glucagon. The reverse effect was observed with insulin-treated rats. Both insulin and glucagon apparently reduced the intracellular esterase turnover in rat liver. Kinetic analysis of the results revealed that insulin mainly lowered the esterase degradation rate, though the rate of esterase synthesis might also have been restricted. In the glucagon-treated rats the de novo synthesis of esterases was strongly reduced.
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PMID:A method for the estimation of esterase synthesis and degradation and its application to evaluate the influence of insulin and glucagon. 39 10

Heats of dilution of concentrated glucagon solutions have been measured calorimetrically at 10 and 25 degrees C in 0.2 M potassium phosphate buffer of pH 10.6. Analysis of the data in terms of a monomer-trimer equilibrium gives the following thermodynamic parameters for the association reaction at 25 degrees C: delta G degrees = 7.34 kcal/mol of trimer, delta H degrees = -31.2 kcal/mol, deltaS degrees = -80 cal/(K mol), deltaCp = 430 cal/(K mol). The sensitivity of heat of dilution data to the association constant and stoichiometry of the reaction is discussed.
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PMID:Thermodynamics of glucagon aggregation. 42 6

The influence of restraint stress on serum calcium (Ca) and phosphate was studied in normal and thyroidectomized rats. In addition the response of gastric stress ulcer index, blood gastrin and glucagon to exogenous Ca was investigated. In intact as well as in thyroidectomized animals serum total, ionised and previously injected radioactive Ca decrease during an 8h stress period, whereas inorganic phosphate increases. Together with a constant specific activity these findings are consistent with hypoparathyroidism and calcitonin independent hypocalcemia during stress. Intragastric infusion of 45 mg/kg Ca-gluconate per 8h proves to be a potent anti-stress ulcer regimen in intact and neck-sham operated, but not in thyroidectomized rats without and with additional adrenal demedullation. Gastrin and glucagon were not correlated with calcemia during either stress alone or stress combined with intragastric Ca infusion. It is suggested that the development of gastric stress ulcerations can be prevented by a Ca-mediated release of endogenous calcitonin.
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PMID:Hypocalcemia during restraint stress in rats. Indication that gastric ulcer prophylaxis by exogenous calcium interferes with calcitonin release. 47 75

Incubation of hepatocytes with [32P]orthophosphate resulted in the incorporation of 32P into material that is precipitated by reaction with antibodies to ATP citrate lyase. The amount of radioactivity precipitated was decreased when unlabeled, purified ATP citrate lyase was added to extracts of hepatocytes that had been incubated with [32P]orthophosphate. Addition of glucagon to hepatocytes that had been preincubated with [32P]orthophosphate resulted in a 56% increase in acid-stable 32P in the trichloroacetic acid-insoluble portion of immunoprecipitates. Catalytic phosphate bound to ATP citrate lyase reaction with ATP and Mg2+ is acid-labile; thus, glucagon-dependent phosphorylation is distinguished from the catalytic phosphate. When hepatocytes were incubated in the absence of [32P]orthophosphate and extracted in a medium containing [gamma-32P]ATP, no acid-stable 32P was present in immunoprecipitates. This indicates that the incorporation into ATP citrate lyase of acid-stable phosphate occurs prior to extraction of the enzyme. Preliminary studies, using a procedure that allows for measurement of enzyme activity starting 1 min after beginning the extraction of lyase from hepatocytes, have shown no difference in lyase activity when hepatocytes are treated with or without glucagon.
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PMID:Phosphorylation of ATP citrate lyase in response to glucagon. 48 38

Rat hepatic pyruvate kinase (type L) has been purified to homogeneity by a simple, rapid procedure involving DEAE-cellulose chromatography and elution from a blue Sepharose column. The enzyme was homogeneous by the criteria of sodium dodecyl sulfate disc gel electrophoresis, had a subunit molecular weight of 57,000, and a specific activity of 558 units/mg of protein at 30 degrees. In order to test whether the enzyme is phosphorylated in vivo, rats were injected with radioactive inorganic phosphate. Incorporation into pyruvate kinase was determined after purification of the enzyme to homogeneity as well as after specific immunoprecipitation of the enzyme from partially purified preparations. Sodium dodecyl sulfate disc gel electrophoresis revealed that 32P was incorporated into the enzyme in both cases. Glucagon administration in vivo resulted in a 200 to 300% increase in the incorporation of 32P into the enzyme which was correlated with an inhibition of enzyme activity and an elevation of hepatic levels of cyclic AMP. These results represent the first demonstration of in vivo phosphorylation of a hepatic glycolytic enzyme and strongly support the hypothesis that glucagon regulates pyruvate kinase activity, at least in part, by a phosphorylation mechanism.
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PMID:Stimulation of glucagon of in vivo phosphorylation of rat hepatic pyruvate kinase. 62 Nov 97

Intravenous application of 1 mg glucagon causes a significant decrease of the magnesium, calcium, and phosphate concentrations in the serum. Concerning the potassium level there is a biphasic change of concentration. Initially a significant increase of the potassium concentration is to be measured which transgresses into a longer phase of decrease of concentration. The possible causes of these changes of electrolytes after application of glucagon are discussed and it is referred to the possible clinical importance. In longer therapeutic application of glucagon a control of the serum parameters of the electrolytes metabolism appears indicated.
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PMID:[The effect of glucagon on serum electrolyte concentrations in man]. 64 44

The trimerization constants of glucagon at pH 10.6 in 0.76 M K2HPO4 have been calculated from circular dichroism data between 5 and 50 degrees C. The free energy, enthalpy, and entropy of transfer have been evaluated from the current results and published data in 0.20 M phosphate. The free energies of transfer are derived completely from an increase in the entropy of transfer, since the enthalpy of transfer is less favorable at all temperatures. These parameters are compared with those of various model groups and compounds: CH2, peptide, methane, ethane, and the 1--13 N-terminal fragments of ribonuclease. The effects of fluoride and chloride on the self-association of glucagon have been compared with that of phosphate at 25 degrees C. These effects are consistent with the binding of approximately one molecule of salt to the trimer and a systematic decrease in the number of water molecules bound to the trimer compared to the monomer for the series K2HPO4, KF, and KCl.
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PMID:Effects of Hofmeister salts on the self-association of glucagon. 64 94


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