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)

In the present study, we used primary cultures of fetal rat hepatocytes which are highly suitable for studying the glycogenic effect of insulin and its regulation. After a lag in the period of culture in the presence of cortisol, glycogenic response to insulin developed together with a progressive accumulation of glycogen. When insulin was added, the rate of glycogen synthesis increased, becoming maximal after 2-3 h, due to the activation of the glycogen synthase system already present. Modification of glycogen precursors in the medium did not alter the amplitude of the insulin effect. The glycogenic effect of insulin was unrelated to that of glucose load and occurred after the formation of glucose-1-phosphate. This only happened when the cyclic AMP-dependent glycogenolytic system was not stimulated, since it was suppressed by low doses of glucagon. Insulin effect, which was time-dependent, ceased after 4 h. This corresponded to a desensitization of hepatocytes without any alteration in the specific binding of insulin. These variations in the glycogenic effect of insulin were likely due to different causes; one of these could be the first events following the interaction of insulin with its receptor.
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PMID:[Expression of the glycogenic response to insulin in cultured fetal hepatocytes]. 634 34

Kinetic constants of glycogen synthase (M0.5 for glucose-6-P and S0.5 for UDP-glucose) were determined after hepatocytes isolated from starved rats were incubated with either glucagon or epinephrine. Incubation with these hormones resulted in an increase in both S0.5 and M0.5. However, the action of glucagon resulted in great modifications on S0.5 whereas epinephrine affected mainly M0.5. Therefore, glucagon and epinephrine alter the kinetic properties of glycogen synthase provoke the phosphorylation of glycogen synthase at different site(s) acting through different mechanisms.
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PMID:Different effects of glucagon and epinephrine on the kinetic properties of liver glycogen synthase. 640 81

Three stages of development of hepatic glycogen metabolism in the rat were studied. These included the last stage of gestation, in which large scale synthesis and accumulation of glycogen takes place, the perinatal period of glycogenolysis, and the suckling period up to and including weaning. The role of insulin in the regulation of the key rate-limiting enzymes of glycogen synthesis (glycogen synthase) and glycogen breakdown (glycogen phosphorylase) was studied as was the role of the key phosphoprotein phosphatase enzymes that regulate activation of synthase (synthase phosphatase) and inactivation of phosphorylase (phosphorylase phosphatase). Glycogen accumulates in significant quantities on days 20-21 of gestation in the rat (term, 22 days). Associated with this increased rate and amount of glycogen accumulation is an increase in glycogen synthase a and synthase phosphatase and phosphorylase phosphatase activities associated with the endoplasmic reticulum (ER). Concomitantly, fetal insulin levels are elevated as is the insulin to glucagon molar ratio and the synthase a/phosphorylase a ratio. At birth, these hepatic glycogen stores are rapidly degraded, and synthase a levels are diminished, as are ER-associated synthase phosphatase and phosphorylase phosphatase activities. Phosphorylase a levels are markedly elevated at this time as well. Insulin levels are decreased, as is the insulin to glucagon molar ratio. Gradually over a period of 4 weeks after birth, glycogen levels increase in the liver, accompanied by increased ER-associated phosphatase activities and an increased insulin to glucagon molar ratio. The data support a role for increased ambient insulin concentrations in regulation of the periods of active glycogen synthesis and accumulation in pre- and postnatal rat liver. A possible site of action of insulin is the ER and associated phosphoprotein phosphatase activities.
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PMID:Regulation of hepatic glycogen metabolism in pre- and postnatal rats. 640 92

32P-labeled perfused rat hearts were used to study the hormonal regulation of glycogen synthase. Following equilibration of perfused hearts with inorganic [32P]phosphate for 30 min, there was an incorporation of approximately 200 pmol of [32P]phosphate/unit of enzyme activity that arose from an exchange of [32P] phosphate with the endogenous [31P]phosphate. Maximum insulin-induced activation (10 milliunits/ml for 5 min), which promoted an I/D activity ratio change from 25% I to 40% I, was associated with a 22% decrease in phosphate content of the enzyme. With hearts from alloxan-induced diabetic animals, there was a 17% higher level of phosphate incorporation and a 4-fold decrease in % I glycogen synthase activity compared to normal animals, but with the diabetic tissue, insulin added to the perfusate had no effect on either the phosphate content or the activity ratio of the enzyme. In perfused hearts from normal animals, DL-isoproterenol and glucagon caused an increase in glycogen synthase phosphorylation of 85-100 pmol/unit of enzyme activity, while L-phenylephrine increased the phosphate content by only 20-35 pmol, but all three hormones caused the same degree of inactivation. The increase in cardiac glycogen synthase phosphorylation induced by DL-isoproterenol, glucagon, and L-phenylephrine was identical, with or without insulin pretreatment; this despite the fact that these three hormones promoted a 3- to 4-fold larger decrease in the enzyme activity ratio with the insulin-treated tissue. In perfused diabetic hearts, DL-isoproterenol, glucagon, and L-phenylephrine caused increased phosphorylation of glycogen synthase without affecting the albeit already low activity ratio of the enzyme. These results show that in the intact perfused heart the same degree of glycogen synthase inactivation can occur as a consequence of differing degrees of phosphorylation, presumably due to phosphorylation at different sites promoted by different second messengers. Conversely, the data indicate that the same extent of phosphorylation, as stimulated by the same second messenger, can inactivate glycogen synthase by different amounts depending upon the prior phosphorylation state of other sites in the protein.
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PMID:Hormonal regulation of the phosphorylation of glycogen synthase in perfused rat heart. Effects of insulin, catecholamines, and glucagon. 641 63

Isolated rat hepatocytes were incubated in a medium containing 0.1 mM [32P]phosphate (0.1 mCi/ml) before exposure to epinephrine, glucagon or vasopressin. 32P-labeled glycogen synthase was purified from extracts of control or hormone-treated cells by the use of specific antibodies raised to rabbit skeletal muscle glycogen synthase. Analysis of the immunoprecipitates by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that a single 32P-labeled polypeptide, apparent Mr 88000, was removed specifically by the antibodies and corresponded to glycogen synthase. Similar electrophoretic analysis of CNBr fragments prepared from the immunoprecipitate revealed that 32P was distributed between two fragments, of apparent Mr 14000 (CB-1) and 28000 (CB-2). Epinephrine, vasopressin or glucagon increased the 32P content of the glycogen synthase subunit. CB-2 phosphorylation was increased by all three hormones while CB-1 was most affected by epinephrine and vasopressin. These effects correlated with a decrease in glycogen synthase activity. From studies using rat liver glycogen synthase, purified by conventional methods and phosphorylated in vitro by individual protein kinases, it was found that electrophoretically similar CNBr fragments could be obtained. However, neither cyclic-AMP-dependent protein kinase nor three different Ca2+-dependent enzymes (phosphorylase kinase, calmodulin-dependent protein kinase, and protein kinase C) were effective in phosphorylating CB-2. The protein kinases most effective towards CB-2 were the Ca2+ and cyclic-nucleotide-independent enzymes casein kinase II (PC0.7) and FA/GSK-3. The results demonstrate that rat liver glycogen synthase undergoes multiple phosphorylation in whole cells and that stimulation of cells by glycogenolytic hormones can modify the phosphorylation of at least two distinct sites in the enzyme. The specificity of the hormones, however, cannot be explained simply by the direct action of any known protein kinase dependent on cyclic nucleotide or Ca2+. Therefore, either control of other protein kinases, such as FA/GSK-3, is involved or phosphatase activity is regulated, or both.
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PMID:Control of glycogen synthase phosphorylation in isolated rat hepatocytes by epinephrine, vasopressin and glucagon. 643 31

The short-term controls of glycogen synthase [EC 2.4.1.11] and glycogen phosphorylase [EC 2.4.1.1] by major regulators, such as insulin, glucose, catecholamine, and glucagon, were compared in a simple, yet organized experimental system, i.e., adult rat hepatocytes in primary culture. Glycogen synthase was activated by glucose markedly and dose-dependently (5-40 mM), but insulin alone (1 X 10(-8) M) activated this enzyme only two-fold. Therefore, activation of the enzyme by the two regulators together was mostly due to activation by glucose. Glucagon at a concentration of 5 X 10(-10) M suppressed this activation almost completely. Glucagon at this concentration activated phosphorylase considerably and this activation was slightly inhibited by insulin. Phenylephrine also activated phosphorylase, and this activation was inhibited by phenoxybenzamine or prazosin, suggesting that activation by catecholamine is through the alpha 1-adrenergic receptor. Similarly a high concentration of glucose diminished the effects of glucagon and phenylephrine. These results suggest that in rat liver, glycogen metabolism is controlled mainly by glucagon, catecholamine, and glucose; the former two activate phosphorylase and inactivate synthase, while glucose activates synthase strongly and inactivates phosphorylase partially. Insulin plays a minor role in both reactions. Thus, the liver is primarily an organ for glucose production, which is regulated by hormones, not for glycogen storage, which is increased only by a high glucose concentration in the portal blood.
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PMID:Glucagon and glucose as major regulators of glycogen metabolism in primary cultured rat hepatocytes. 643 74

Hepatic glycogen metabolism was studied in rats during the period of transition from the fed to fasted states. Glycogenic activity was measured in vivo based on the incorporation of [14C]glucose into liver glycogen. Its changes were almost parallel to the changes in glycogen synthase activity. Progressive accumulation of liver glycogen that occurred in the fed state was associated with a proportional increase in glycogenic activity. Within 4 h after the cessation of food intake, glycogenic activity showed a precipitous fall from the peak to its nadir without significant changes in glycogen content. Meanwhile, the glucose concentration in the portal vein decreased. Upon further development of fasting, glycogenic activity displayed a progressive regain, reciprocally as glycogen contents gradually decreased. The precipitous fall of glycogenic activity during the transition from the fed to fasted states was associated with a transient increase in plasma glucagon, and was partly overcome by the injection of anti-glucagon serum. It is concluded that the fall of portal venous concentration of glucose and secretion of glucagon act as a signal to initiate liver glycogen metabolism characteristic of the fasted or postabsorptive state.
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PMID:Glycogen metabolism in rat liver during transition from the fed to fasted states. 677 87

The effects of vasoactive intestinal polypeptide (VIP) on several enzymes of glycogen metabolism in rat hepatocytes were compared with those of glucagon and of vasopressin (ADH). VIP caused phosphorylase activation and glycogenolysis in hepatocytes from fed rats. In hepatocytes from fasted rats incubated with glucose, lactate, and pyruvate, VIP inhibited net glycogen deposition, inactivated glycogen synthase, and activated phosphorylase. VIP was about 100-fold less potent than glucagon and 1,000-fold less potent than ADH in causing activation of phosphorylase. The ability of VIP to activate phosphorylase was not altered by chelation of the calcium in the medium. The half maximal effective doses of VIP for both phosphorylase activation and stimulation of glycogenolysis were 10-30 nM. Treatment with VIP, ADH, or glucagon did not decrease phosphorylase phosphatase activity. Each of these hormones, however, lengthened the lag time before synthase phosphatase activity was expressed in vitro. Other gut hormones tested did not affect hepatocyte glycogen metabolism. These results do not support the concept of physiologic control of hepatic glycogen metabolism by VIP or by other gut hormones.
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PMID:Effect of vasoactive intestinal polypeptide on glycogen metabolism in rat hepatocytes. 680 98

(+)- and (-)-catechin showed opposite effects on glycogen metabolism in isolated rat hepatocytes. Addition of 0.5 mM catechin to hepatocytes from fasted rats resulted in the case of the (+)-isomer in a 90% stimulation and the case of the (-)-isomer in a 90% inhibition of net glycogen production. When 0.5 mM of the two isomers were added to hepatocytes from fed rats, (+)-catechin inhibited glycogenolysis by 33%, whereas the (-)-isomer stimulated the same process by 42%. At equal concentrations, the effects of (-)-catechin were stronger than those of the (+)-isomer. (-)-Epicatechin acted in a manner similar to (+)-catechin; however, the effect was less pronounced. (+)-Catechin antagonized the inhibitory action of suboptimal doses of glucagon on glycogen production whereby no change in basal or glucagon-elevated cyclic AMP level was observed. The activities of glycogen synthase a and glycogen phosphorylase a were changed by (+)- and (-)-catechin in a way corresponding to the changes in glycogen production and breakdown. (-)-Catechin, however, stimulated the activities of both glycogen synthase a and glycogen phosphorylase a in hepatocytes from fed rats. A possible interaction of the flavonoids or of their metabolites with glycogen phosphorylase is discussed.
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PMID:Stereospecific effects of (+)- and (-)-catechin on glycogen metabolism in isolated rat hepatocytes. 687 Dec 57

Rats from an inbred strain (NZR/Mh) were found to have high concentrations of glycogen in their livers, even after 24 h of starvation. Despite this, blood glucose concentrations were well maintained on starvation for up to 72 h. The primary defect is a deficiency of liver phosphorylase kinase, causing a lack of active glycogen phosphorylase, although total phosphorylase is normal. The intravenous injection of glucagon caused a rapid activation of cyclic AMP-dependent protein kinase in the liver, but no increase in either phosphorylase kinase or phosphorylase a activity. Although total glycogen synthase activity in the livers of affected rats was higher than normal, glycogen synthase in the active form was very low, presumably as a result of the high liver glycogen content. The condition is transmitted as autosomal recessive and, apart from hepatomegaly, the affected rats appear healthy.
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PMID:Glycogen-storage disease in rats, a genetically determined deficiency of liver phosphorylase kinase. 693 96


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