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

We have studied the effect of Vasoactive Intestinal Peptide (VIP) on glycogenolysis and gluconeogenesis (as measured by the conversion of [U-14C]pyruvate into glucose) in hepatocytes isolated from fed rats. The influence of VIP on glycogen phosphorylase alpha and pyruvate kinase activities, as well as on cAMP levels, was also evaluated. In addition, the possible antagonism of insulin on these VIP-mediated effects was investigated. VIP enhanced both glycogenolysis and gluconeogenesis in a dose-dependent manner. At 10(-6) M VIP, both processes were increased 2-fold as compared to the basal values; the calculated half-maximal stimulatory concentrations were 2.5 x 10(-8) M and 4 x 10(-8) M, respectively. VIP also caused a dose-dependent activation of glycogen phosphorylase and inactivation of pyruvate kinase. At 10(-6) M VIP, glycogen phosphorylase a was increased 3-fold and pyruvate kinase activity was reduced by 46%. The addition of 10(-7) M VIP to the incubation medium caused a 2-fold increase of basal cAMP levels. All these VIP-mediated effects were markedly blocked by the presence of 10(-8) M insulin. As compared to glucagon (10(-7) M) the potency of an equimolar concentration of VIP, in terms of stimulation of gluconeogenesis, inactivation of pyruvate kinase, and activation of glycogen phosphorylase ranged from 35-45%. Our results indicate that VIP increases hepatic glucose output through the stimulation of both glycogenolysis and gluconeogenesis. These effects seem to be mediated by a cAMP-dependent mechanism.
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PMID:Stimulatory effect of vasoactive intestinal peptide on glycogenolysis and gluconeogenesis in isolated rat hepatocytes: antagonism by insulin. 634 59

A detailed study of the control of liver pyruvate dehydrogenase activity by various hormones was carried out with perfused liver and isolated hepatocytes. Vasopressin produced a significant increase in the enzyme activity in fed rats, and the time course and sensitivity of the response was similar to that of glycogen phosphorylase a. The enzyme from starved animals was resistant to hormonal activation. The possible factors involved in the above effects are discussed. Angiotensin and phenylephrine also increased pyruvate dehydrogenase activity, and the magnitude of the response was of the same order as that to vasopressin by the liver enzyme. The effects of these hormones on pyruvate dehydrogenase activity were critically dependent on extracellular Ca2+, thus suggesting a role for this ion in the mechanism of action of the hormones. Insulin did not appear to have a role in the control of the enzyme activity, as shown by its lack of effect on the enzyme. Glucagon, in contrast with previous reports, produced a rapid, transient and significant increase in pyruvate dehydrogenase activity. The physiological importance of the above effects is discussed.
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PMID:Hormonal control of pyruvate dehydrogenase activity in rat liver. 639 71

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

Tumor hypoglycemia induced by a heterotransplantable human ovarian carcinoma line (OCL-1) was described. Plasma glucose decreased to 36 +/- 9 mg/dl (S.D.) at 8 to 12 weeks after the transplantation. Significant amounts of immunoreactive insulin and insulin-like active substance could not be detected in tumor tissues. Plasma immunoreactive insulin levels were low, and glucagon levels were high in OCL-1-bearing nude mice, compared with the control. Light- and electron-microscopically, tumor cells possessed large amounts of glycogen, and this finding was also biochemically confirmed. OCL-1 tumor showed high glycogen synthetase activity compared with other control tumors, while glycogen phosphorylase activity was the same level as other tumors. The high glycogen synthetase activity was considered to be the cause of glycogen accumulation in tumor cells. Hypoglycemia in OCL-1-bearing nude mice was considered to be caused by abnormal redistribution of glycogen, i.e., marked accumulation of glycogen in tumor tissues and depletion of glycogen in the host liver. This OCL-1 tumor-nude mice system was thought to be a good model for research on the mechanisms of tumor hypoglycemia occurring in cancer patients with nonpancreatic islet cell tumors.
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PMID:Tumor hypoglycemia induced in nude mice by a heterotransplantable human ovarian carcinoma line (OCL-1). 642 51

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

(+)- 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

1. Glucagon, epinephrine, norepinephrine, isoproterenol and phenylephrine each increases significantly glucose appearance and glycogen disappearance from hepatocytes of both juvenile and adult fed rabbits. Such increases caused by catecholamines and adrenergic agonists are suppressed significantly by the beta-adrenergic antagonist propranolol but are unchanged by the alpha-antagonist phentolamine. 2. Glucagon, epinephrine, norepinephrine, isoproterenol and phenylephrine each increases significantly glycogen phosphorylase a activity and decreases significantly the pyruvate kinase activity ratio (assayed with 0.8 mM phosphoenolpyruvate +/- 200 microM fructose 1,6-bisphosphate) in hepatocytes from both juvenile and adult rabbits. Changes induced by catecholamines and adrenergic agonists in the activities of both enzymes are significantly diminished by propranolol but unaltered by phentolamine. 3. These observations suggest that regulation of glycogenolysis and gluconeogenesis in rabbits by glucagon and catecholamines is at least partially due to activation of glycogen phosphorylase and inhibition of pyruvate kinase. Contrary to the age-related changes observed in the adrenergic nature of catecholamines' regulation of these two processes in rats, such regulation of both processes by catecholamines is beta-adrenergic in rabbits regardless of age.
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PMID:The influences of glucagon, epinephrine and adrenergic agents on glycogen phosphorylase a and pyruvate kinase activities in hepatocytes from juvenile and adult rabbits. 710 86

We have examined the possible influence of bovine pancreatic polypeptide (bPP) on glycogenolysis and gluconeogenesis in hepatocytes isolated from fed rats. The activity of glycogen phosphorylase a and pyruvate kinase, enzymes implicated in the hormonal regulation of these pathways, was also measured. Glycogenolysis was estimated by glucose release into the medium and gluconeogenesis by (U-14C) pyruvate incorporation into glucose. Addition of bPP to the incubation medium did not modify endogenous glucose production or glycogen phosphorylase a activity, either under basal conditions or on stimulation by glucagon (3 x 10(-10) M) or phenylephrine (10(-5) M). bPP also failed to alter both the incorporation rate of (U-14 C) pyruvate into glucose and pyruvate kinase activity, under basal conditions as well as in the presence of glucagon. Furthermore, time-course experiments revealed no effect of bPP on glycogen phosphorylase a or pyruvate kinase activities. These data indicate that pancreatic polypeptide is not implicated in the control of glucose production by isolated liver cells from fed rats.
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PMID:Lack of effect of bovine pancreatic polypeptide on glucose production by isolated rat hepatocytes. 710 44

Using rat liver hepatocytes, we studied the effect of the tyrosine kinase inhibitor genistein on the Ca2+/IP3 (inositol 1,4,5-trisphosphate) and the cAMP (adenosine 3:5-cyclic monophosphate) transduction mechanisms. Genistein specifically blocked the activation of glycogen phosphorylase after EGF (epidermal growth factor). Genistein on its own partially activated phosphorylase and inactivated glycogen synthase. Genistein did not influence levels of IP3, but increased those of cAMP. This was especially clear when genistein was given together with glucagon. The data suggest an effect of a tyrosine kinase on the synthesis/degradation of cAMP.
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PMID:Effect of genistein on both basal and glucagon-induced levels of cAMP in rat hepatocytes. 748 48


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