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

Acute hormonal effects on the synthesis rate of the cytosolic form of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (GTP), were investigated using rat hepatocytes maintained in short-term suspension culture. Cells were pulse-labeled with [3H]leucine or [35S]methionine and the rate of synthesis of phosphoenolpyruvate carboxykinase was estimated after immunoprecipitation of cell extracts with specific antibodies or following high-resolution two-dimensional gel electrophoresis of cell proteins. Total RNA was also extracted from cultured cells and subsequently translated in a wheat germ cell-free protein-synthesis system, in order to quantify the level of functional mRNA coding for phosphoenolpyruvate carboxykinase. Glucagon, the single most effective inducer, causes a 15--20-fold increase in the level of specific mRNA in 2 h, accompanied by a similar increase in enzyme synthesis rate. The extent of induction is further amplified about threefold when dexamethasone is added to the culture medium. The synergistic action of dexamethasone does not require pre-exposure of the cells to the glucocorticoid, but on the contrary occurs without lag upon simultaneous addition of glucagon and dexamethasone. The induction of phosphoenolpyruvate carboxykinase mRNA by glucagon is markedly depressed in hepatocytes inhibited for protein synthesis by cycloheximide. Cycloheximide-inhibited cells, however, display a considerable induction of the message after joint stimulation with dexamethasone and glucagon. Thus, the synergistic action of dexamethasone does not require concomitant protein synthesis. These data provide indirect evidence for a primary effect of the glucocorticoids on the expression of the phosphoenolpyruvate carboxykinase gene. Besides glucagon and dexamethasone, the thyroid hormones are shown to influence the rate of phosphoenolpyruvate carboxykinase synthesis in isolated liver cells. The stimulatory effect of 3,5,3'-triiodothyronine (T3) is best demonstrated as a twofold increase in relative rate of enzyme synthesis in cells supplied with T3 plus glucagon, as compared to cells challenged with glucagon alone. The effect of T3 relies on a pretranslational mechanism, as shown by a commensurate increase in functional mRNA coding for phosphoenolpyruvate carboxykinase. Dose-response experiments with T3 as well as dexamethasone demonstrate effects at very low hormone levels, consistent with a role for these hormones as physiological modulators of phosphoenolpyruvate carboxykinase expression.
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PMID:Effects of glucagon, dexamethasone and triiodothyronine on phosphoenolpyruvate carboxykinase (GTP) synthesis and mRNA level in rat liver cells. 651 Apr 13

Hepatocytes prepared from rats treated with dexamethasone for 2 or 3h and maintained in the presence of 10 microM-dexamethasone in the preparation and incubation buffers showed significantly elevated rates of gluconeogenesis compared with those prepared from control animals. Dexamethasone treatment also increased the sensitivity of the cells to glucagon and the catecholamines. Analysis of the concentrations of metabolites in the gluconeogenic pathway indicated that dexamethasone decreased the intracellular concentration of pyruvate and increased those of phosphoenolpyruvate, acetyl-CoA and citrate, suggesting a stimulation of the reaction(s) converting pyruvate into phosphoenolpyruvate. This was substantiated by analysis of the pattern of metabolites found in the mitochondrial compartment after digitonin fractionation of the cells. Inclusion of 3-mercaptopicolinate in the incubation enhanced the effect of the hormone on the distribution of metabolites. Thus, in the absence of an effect of the steroid at the level of phosphoenolpyruvate carboxykinase or pyruvate kinase, dexamethasone treatment still increased the formation of malate, aspartate and citrate from pyruvate, indicating a stimulation in the intact cell of pyruvate carboxylase. It is suggested that the stimulation of pyruvate carboxylase is a result of a general activation of mitochondrial function, with an increase in the intramitochondrial concentrations of acetyl-CoA and ATP, a decrease in glutamate and an enhanced intramitochondrial [ATP]/[ADP] ratio.
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PMID:Effect of treatment of rats with dexamethasone in vivo on gluconeogenesis and metabolite compartmentation in subsequently isolated hepatocytes. 672 48

Adult rat hepatocytes were kept in primary culture for 48 h under different hormonal conditions to induce an enzyme pattern which with respect to carbohydrate metabolism approximated that of periportal and perivenous hepatocytes in vivo. 1. Glucagon-treated cells compared with control cells possessed a lower activity of glucokinase, a 4.5-fold higher activity of phosphoenolpyruvate carboxykinase and unchanged levels of glucose-6-phosphatase, phosphofructokinase, fructose-bisphosphatase and pyruvate kinase; they resembled in a first approximation the periportal cell type and are called for simplicity 'periportal'. Inversely, insulin-treated cells compared with control cells contained a 2.2-fold higher activity of glucokinase, a slightly decreased activity of phosphoenolpyruvate carboxykinase, increased activities of phosphofructokinase and pyruvate kinase and unaltered levels of glucose-6-phosphatase and fructose-bisphosphatase; they resembled perivenous cells and are called simply 'perivenous'. Gluconeogenesis and glycolysis were studied under various substrate and hormone concentrations. 2. Physiological concentrations of glucose (5 mM) and lactate (2 mM) gave about 80% saturation of gluconeogenesis from lactate and less than 15% saturation of glycolysis at a simultaneous 40% inhibition of the glycolytic rate by lactate. 3. Comparison of the two cell types showed that under identical assay conditions (5 mM glucose, 2 mM lactate, 0.5 nM insulin, 0.1 muM dexamethasone) gluconeogenesis was 1.5-fold faster in the 'periportal' cells and glycolysis was 2.4-fold faster in the 'perivenous' cells. 4. Metabolic rates were under short-term hormonal control. Insulin increased glycolysis three fold in both cell types with a half-maximal effect at about 0.4 nM, but did not influence the gluconeogenic rate. Glucagon inhibited glycolysis by 70% with a half-maximal effect at about 0.1 nM. Gluconeogenesis was stimulated by glucagon (half-maximal dose: 0.5 nM) 1.8-fold only in 'periportal' cells containing high phosphoenolpyruvate carboxykinase activity, not in the 'perivenous' cells with a low level of this enzyme. 5. A comparison of the two cell types showed that with maximally stimulating hormone concentrations gluconeogenesis was threefold faster in 'periportal' cells and glycolysis was eightfold faster in 'perivenous' cells. The results support the view that periportal and perivenous hepatocytes in vivo catalyse gluconeogenesis and glycolysis at inverse rates.
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PMID:Induction in primary culture of 'gluconeogenic' and 'glycolytic' hepatocytes resembling periportal and perivenous cells. 675 22

Phosphoenolpyruvate carboxykinase was localized in rat liver parenchyma, as well as isolated and cultured hepatocytes by indirect immunofluorescence microscopy using antibodies against the enzyme raised in rabbits and purified by antigen-affinity-chromatography. 1. In fed and fasted rats the enzyme was heterogeneously distributed over the parenchyma. It was predominantly located in the periportal zone. 2. In hepatocytes shortly after isolation or cultured for 1 h the heterogeneity with respect to the enzyme content was maintained. 3. In hepatocytes cultured for 24 h and treated with glucagon the heterogeneity was lost. The results indicate that the heterogeneity of hepatocytes as to phosphoenolpyruvate carboxykinase content is due to a different expression of the genome.
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PMID:Heterogeneous distribution of phosphoenolpyruvate carboxykinase in rat liver parenchyma, isolated, and cultured hepatocytes. 675 28

Experiments were designed to estimate the effect of in vivo hormonal treatment of rats on serine metabolism in isolated hepatocytes by incubating hepatocytes in the presence or absence of 3-mercaptopicolinic acid (a potent inhibitor of phosphoenolpyruvate carboxykinase), the relative flow of [14C]serine carbon to [14C]glucose via the serine dehydratase (SDH)-initiated vs. serine amino-transferase (SAT-initiated pathways could be estimated. Streptozotocin-induced diabetes caused a tripling of the absolute rate of [14C]serine conversion to [14C]glucose, along with a shift in the relative importance of the SAT-mediated pathway. Hydrocortisone treatment had no significant effect on either the rate or route of serine metabolism. The SAT-mediated pathway was the major route of serine conversion to glucose after 4 days of chronic glucagon injections, although the absolute rate of conversion was enhanced by only 50%. This was the only treatment examined in which SDH was not the major route for serine gluconeogenesis. The enzyme activity responses of SDH and SAT to hormonal manipulation previously reported do not necessarily reflect the observed changes in pathway flux reported in the present study.
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PMID:Effects of in vivo hormonal treatment on serine metabolism in isolated rat hepatocytes. 680 68

The mitochondrial and cytosolic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase(transphosphorylating), EC 4.1.1.32) occurring in the bullfrog (Rana catesbeiana) liver were studied. The enzymes in th two intracellular compartments of both tadpole and adult frog liver were immunologically identical. Both radioactively-labelled forms of the mitochondrial and cytosolic phosphoenolpyruvate carboxykinase from bullfrog liver were imported at the same rate into intact mitochondria in vitro. The mitochondrial and cytosolic enzyme activities did not respond to the administration of glucagon, glucocorticoid, quinolinate and D-mannoheptulose which are known as enhancers of phosphoenolpyruvate carboxykinase, but were found to increase during natural metamorphosis. The former activity was markedly increased in the tadpoles treated with 3,5,3'-triiodothyronine. It was supposed that in the bullfrog liver the phosphoenolpyruvate carboxykinase localized in the mitochondria is of central importance in phosphoenolpyruvate synthesis from oxaloacetate.
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PMID:Cytosolic and mitochondrial phosphoenolpyruvate carboxykinase of the bullfrog, Rana catesbeiana, liver. 697 Nov 27

Phloridzin, an inhibitor of renal sugar transport, produces an important loss of glucose in urine of treated animals. In order to reduce severely the maternal glucose supply to the fetuses in short-term experiments, we have combined phloridzin administration to pregnant rats with 18 h starvation. Fetuses from starved phloridzin-treated mothers were compared with fetuses from starved mothers. Combined treatment markedly decreases fetal blood glucose concentration (-36%) and fetal liver glycogen stores (-76%). These changes are associated with a decrease in plasma insulin (-25%), a rise in plasma glucagon (+120%) and a marked increase of hepatic PEPCK activity (+400%). It appears from these results that phloridzin treatment for a short duration is able to induce glycogenolysis and the premature appearance of PEPCK in the liver of rat fetuses.
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PMID:Fetal metabolic response to phloridzin-induced hypoglycemia in pregnant rats. 699 14

Plasma hormones, glucose and free fatty acids, liver glycogen and two key enzymes of glycolysis and gluconeogenesis were examined in adult rats during a 40-day period of high protein feeding. Plasma insulin fell within 1 day but returned to normal after 4 days. Glucagon changed more slowly, reaching a maximum on day 4 and declined to near the control value within 24 days. Consequently, the insulin to glucagon ratio was lower on days 1, 4 and 8 and was nearly normal on day 24. With respect to hepatic enzymes, phosphoenolpyruvate carboxykinase activity rose sharply on the 1st day and remained elevated for 40-day period; the L-isozyme of pyruvate kinase, although unchanged on the 1st day, decreased thereafter and from day 8 on represented 15--20% of control. Circadian variations in these parameters were also measured in rats adapted to the high protein diet. In such animals, the diurnal change in plasma hormones was less marked but tended to be inverted with respect to controls; the insulin/glucagon ratio was highest during daylight on high protein and in late night on the control diet. Over 24 hours, pyruvate kinase activity was related directly and phosphoenolpyruvate carboxykinase inversely to the hormone ratio. We concluded that in rats adapted to high protein, as in controls, the diurnal balance between glycolysis and gluconeogenesis is probably regulated by the same factor, namely the insulin/glucagon ratio.
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PMID:Plasma glucagon and insulin concentrations and hepatic phosphoenolpyruvate carboxykinase and pyruvate kinase activities during and upon adaptation of rats to a high protein diet. 701 97

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

Continuous glucose infusion was used to induced mild hyperglycaemia in unrestrained pregnant rats during the last three days of pregnancy. Control pregnant rats were infused with distilled water. Fetuses were studied after normal or prolonged pregnancy. Fetuses from glucose-infused rats, compared with controls, showed higher plasma glucose levels, increased plasma insulin and lower plasma glucagon concentrations. Pregnancy prolonged until day 23.5 resulted in a rise in the glucagon/insulin ratio from 6.5 to 67 in fetuses from control rats and from 1.3 to 13 in fetuses from glucose-infused rats. Concurrently in fetuses from control rats, liver phosphoenolpyruvate carboxykinase activity increased markedly and liver glycogen stores decreased sharply. In fetuses from glucose-infused rats, liver phosphoenolpyruvate carboxykinase activity rose and glycogen content decreased, but to a lesser extent. These results show that both the A and B cells of the rat fetal pancreas are sensitive to chronic glucose stimulation.
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PMID:Hyperglycaemia induced by glucose infusion in the unrestrained pregnant rat during the last three days of gestation: metabolic and hormonal changes in the mother and the fetuses. 704 Jan 46


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