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)

The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue.
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PMID:Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans. 16 65

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

Hepatocyte-hepatoma hybrid cells were obtained by fusion of hepatocytes from adult rats and Fao hepatoma cells in the presence of polyethylene glycol. These hybrids were called hepatocytoma cells. The preservation of liver-specific enzyme activities and metabolic functions was studied in the hybrid clone 1E3. 1) The proliferating hepatocytoma cells formed monolayers presenting morphological similarity to primary cultures of hepatocytes. 2) In contrast to Fao hepatoma cells, activities of all gluconeogenic key enzymes were preserved at normal or reduced levels. 3) Lactate-dependent glucose formation was maintained at a state reduced to 36% of the gluconeogenesis in hepatocytes; no glucose formation was detected in Fao hepatoma cells. 4) The activity of the liver-specific glucokinase was reduced in hepatocytoma cells, but it was still present in contrast to Fao cells. The liver-specific isoenzyme pyruvate kinase type L was replaced by the isoenzyme type M2. 5) Gluconeogenic and glycolytic enzyme activities were regulated in hepatocytoma cells by glucagon (0.1 microM) and by insulin (0.1 microM). 6) The genome of hepatocytoma cells and its expression were stable for at least one year, when spontaneously dedifferentiating cells were removed by recloning in hypoxanthine-aminopterine-thymidine (HAT) medium.
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PMID:Hormone-sensitive carbohydrate metabolism in rat hepatocyte-hepatoma hybrid cells. 132 97

1. In sepsis various processes of carbohydrate metabolism, such as hepatic gluconeogenesis and glycolysis, are altered. Phosphofructokinase-1, a key glycolytic enzyme, is controlled in the long term via regulation of synthesis and degradation of the protein itself, while in the short term it is regulated by allosteric effectors, such as fructose 2,6-bisphosphate (the most potent). In the present study hepatic phosphofructokinase-1 activity as well as phosphofructokinase-2 activity and the concentration of fructose 2,6-bisphosphate were assayed to determine if they might contribute to the derangement of carbohydrate metabolism seen commonly in sepsis. 2. The levels of glycogen and fructose 2,6-bisphosphate and the activity of phosphofructokinase-1 and phosphofructokinase-2 were determined in hepatic biopsies obtained at laparotomy from six patients with and seven patients without abdominal septic foci. 3. A significant increase in plasma lactate concentration was observed in the septic patients, whereas no significant differences in tissue glycogen content or plasma glucose concentration were seen between the groups. 4. No significant change in plasma insulin concentration was observed. However, levels of the counter-regulatory hormones (glucagon, cortisol and adrenaline) were elevated in the septic patients. 5. A 60% decrease in hepatic phosphofructokinase-1 activity was seen in the septic patients. However, no significant changes in hepatic phosphofructokinase-2 activity and fructose 2,6-bisphosphate content were observed in the septic patients. 6. The present results demonstrate that the decrease in hepatic phosphofructokinase-1 activity occurring in sepsis does not appear to reflect alterations in the concentration of fructose 2,6-bisphosphate.
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PMID:Hepatic phosphofructokinase-1 activity and fructose 2,6-bisphosphate levels in patients with abdominal sepsis. 185 Jun 80

Pyruvate kinase (PK), an important glycolytic enzyme, has two genes per haploid genome in mammals and each gene encodes two isozymes. The L gene produces the L- and R-types using alternative promoters. The M gene generates the M1- and M2-types by alternative RNA splicing. Expression of the PK isozymes is tissue-specific and regulated developmentally. Carcinogenesis apparently reverses the developmental process. Expression of the L-type is regulated by dietary and hormonal factors. These regulations occurred at post-transcriptional as well as transcriptional levels. The transcription of hepatic L-type PK is stimulated by insulin and inhibited by glucagon. The insulin action requires ongoing protein synthesis and metabolism of glucose, and is enhanced by glucocorticoid. Dietary fructose also stimulates expression of the L-type in liver, kidney, and small intestine, but its mechanism is dependent on tissues, and on plasma insulin levels in the case of the liver. In normal liver, the fructose induction is explained by stimulation of gene transcription. On the other hand, fructose acts mainly at the post-transcriptional level in diabetic liver and other tissues. These fructose effects are attributable to common metabolite(s) of fructose and glycerol. Studies on transgenic mice indicate that the 5'-flanking region up to -3 kb of the L-type PK gene contains cis-acting elements responsible for insulin regulation and tissue-specific expression of the L-type. Further analysis using a transient expression assay revealed the presence of multiple elements necessary for expression of the L-type in hepatocytes in the region up to -170b.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Regulation of pyruvate kinase gene expression and its clinical application]. 223 46

Altered glucose metabolism is one of the commonly observed sequelae of sepsis and septic shock. The present investigation was undertaken to determine the role of endotoxin (ET) upon hepatocyte glucoregulation, by measuring the activity of pyruvate kinase (PK), a key glycolytic enzyme. Hepatocytes were exposed to endotoxin concentrations known to occur in vivo during sepsis, i.e., from 1 X 10(-14) to 1 X 10(-8) g/ml. The alteration of the enzyme activities after addition of epinephrine, glucagon, insulin and calcium ionophore A23187 with and without ET preincubation were also examined. ET alone decreased the PK activity by 12% at all concentrations tested. The basal inhibition of the enzyme caused by epinephrine (-48%) was partially blocked by ET preincubation above 1 X 10(-10) g/ml. There were no ET-(glucagon, calcium ionophore, insulin) interaction. These in vitro results do not support pyruvate kinase as a site of hepatic enzyme regulation defect in endotoxaemia.
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PMID:Endotoxin, epinephrine, glucagon, insulin and calcium ionophore A23187 modulation of pyruvate kinase activity in cultured rat hepatocytes. 226 25

The influence of insulin and glucagon on the release of glycolytic enzyme activities and actin from cultured pig kidney cells treated with digitonin has been studied. Both insulin and glucagon reduced the release of all glycolytic enzymes except for phosphofructokinase, and concurrently reduced the release of actin. These data have been discussed in relation to their contribution to knowledge of the interactions between glycolytic enzymes and actin filaments of the cytoskeleton, and to the influence of hormones on these interactions.
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PMID:The influence of insulin and glucagon on the interactions between glycolytic enzymes and cellular structure. 304 65

We have used control analysis to quantify the distribution of control in the gluconeogenic pathway in liver cells from starved rats. Lactate and pyruvate were used as gluconeogenic substrates. The flux control coefficients of the various enzymes in the gluconeogenic pathway were calculated from the elasticity coefficients of the enzymes towards their substrates and products and the fluxes through the different branches in the pathway. The elasticity coefficients were either calculated from gamma/Keq. ratios (where gamma is the mass-action ratio and Keq. is the equilibrium constant) and enzyme-kinetic data or measured experimentally. It is concluded that the gluconeogenic enzyme pyruvate carboxylase and the glycolytic enzyme pyruvate kinase play a central role in control of gluconeogenesis. If pyruvate kinase is inactive, gluconeogenic flux from lactate is largely controlled by pyruvate carboxylase. The low elasticity coefficient of pyruvate carboxylase towards its product oxaloacetate minimizes control by steps in the gluconeogenic pathway located after pyruvate carboxylase. This situation occurs when maximal gluconeogenic flux is required, i.e. in the presence of glucagon. In the absence of the hormone, when pyruvate kinase is active, control of gluconeogenesis is distributed among many steps, including pyruvate carboxylase, pyruvate kinase, fructose-1,6-bisphosphatase and also steps outside the classic gluconeogenic pathway such as the adenine-nucleotide translocator.
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PMID:Control of gluconeogenesis in rat liver cells. Flux control coefficients of the enzymes in the gluconeogenic pathway in the absence and presence of glucagon. 380 Aug 95

The influences of IAP on the residual pancreatic endocrine function and carbohydrate metabolism after extensive pancreatectomy in the rat were studied with oral glucose tolerance test (OGTT), arginine tolerance test (ATT), and measurement of hepatic glycogen, and hepatic glycolytic enzyme activity, and histological examination, etc. Wistar male rats weighing around 300 g were divided into the groups with IAP treatment and without it, and in the group with IAP treatment IAP 10 micrograms/kg was administered without anesthesia via the tail vein. In each group 60 and 90% pancreatectomies were performed in accordance with Scow's method, and the simple laparotomy group was used as control. Slight abnormality of glucose tolerance was shown in 60% pancreatectomy. The abnormality became worse with time in 90% pancreatectomy. Glucagon secretion was not damaged markedly even after extensive pancreatectomy. IAP stimulated IRI secretory response and improved glucose tolerance in 60% pancreatectomy group. IAP showed no effect in 90% pancreatectomy group. IAP did not stimulate IRG secretory response after pancreatectomy. Hepatic glycolytic enzyme activity was high in the group with IAP treatment. From the above observation, it has been suggested that IAP may be indicated for the abnormal carbohydrate metabolism after pancreatectomy, if pancreatectomy is not too extensive.
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PMID:[Experimental study on carbohydrate metabolism and pancreatic endocrine function after pancreatectomy--influence of islet activating protein (IAP)]. 396 25

It has been previously demonstrated that the enteric hormone glucagon-like peptide-1 (7-36 amide) (GLP-1) has acute effects on glucose-induced insulin secretion by RIN 1046-38 cells. In this study, we investigated the effects of extended exposure of RIN 1046-38 cells to GLP-1 and examine the mechanism by which GLP-1 synergizes with glucose in stimulating insulin secretion. Compared with cells cultured with glucose alone, incubation of cells with glucose plus 1 or 10 nM GLP-1 for 12 or 24 h significantly increased insulin release by about 3-fold, intracellular insulin content by 1.5-fold, and insulin messenger RNA (mRNA) by almost 2.5-fold. The insulinotropic effects of GLP-1 on RIN 1046-38 cells were accompanied by an up-regulation of both glucose transporter-1 (GLUT-1) and hexokinase I mRNA by about 2-fold. mRNA levels of GLUT-2 and glucokinase, which were low in controls, were unchanged by GLP-1 treatment. Treatment of cells with a transcription inhibitor, actinomycin D, demonstrated that elevated insulin mRNA levels after a GLP-1 exposure are mainly due to stabilization of the mRNA. In contrast, the elevated mRNA levels of GLUT-1 and hexokinase I are the result of increased transcription stimulated by GLP-1 exposure. Actinomycin D blunted the GLP-1 effect on insulin release but did not affect GLP-1 mediated elevation of insulin mRNA. This suggests that actinomycin D inhibits the transcription of the proteins necessary for insulin biosynthesis and insulin release, such as GLUT-1 and hexokinase I. Our study suggests that the mechanisms by which extended exposure of RIN 1046-38 cells to GLP-1 increases glucose-stimulated insulin secretion include significant up-regulation of glucose-sensing elements.
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PMID:Glucagon-like peptide-1 affects gene transcription and messenger ribonucleic acid stability of components of the insulin secretory system in RIN 1046-38 cells. 758 24


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