Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kinetic evidence of a time- and dose-dependent inactivation of phosphofructokinase by glucagon in isolated rat hepatocytes is reported. This inactivation, which persists after gel filtration of a cell-free extract on Sephadex G-25 and after 400-fold purification of the enzyme on agarose-ATP, is observed when the enzyme activity is measured at subsaturating concentrations of fructose 6-phosphate, while there is no change in Vmax. Phosphofructokinase inactivation by glucagon parallels the known inactivation of pyruvate kinase L and activation of glycogen phosphorylase alpha. Exogenous cyclic AMP mimics the effect of this hormone. Half-maximal effect for both phosphofructokinase and pyruvate kinase L is caused by a similar dose of glucagon (1 x 10(-10) M). The inactivation of phosphofructokinase by nonsaturating concentration of glucagon is reversed spontaneously within 40 min of incubation and this reversion is accelerated by insulin.
 ...
PMID:Inactivation of phosphofructokinase by glucagon in rat hepatocytes. 15 82

The effects of intravenous glucose, insulin and glucagon admininistration on the hepatic glycogen synthase and glycogen phosphorylase systems were assessed in the anesthetized rhesus monkey. Results were correlated with measurements of hepatic cyclic AMP (cAMP) concentrations and plasma glucose, insulin, and glucagon concentrations. Both glucose and insulin administration promoted significant inactivation of phosphorylase by 1 min, which was followed by more gradual activation of synthase. Neither glucose nor insulin caused significant changes in hepatic cAMP. Marked hyperglucagonemia resulting from insulin-induced hypoglycemia did not cause increases IN in hepatic cAMP, suggesting that the elevated insulin levels possibly inhibited glucagon action on the hepatic adenylate cyclase-cAMP system. Glucagon administration caused large increases in hepatic cAMP and activation of phosphorylase within 1 min, followed by more gradual inactivation of synthase when it had been previously activated by glucose. Concomitant glucose infusion, with resulting increased plasma insulin concentrations, markedly diminished the duration of hepatic cAMP elevations following glucagon adminstration, again suggesting an insulin inhibition of glucagon action on the hepatic adenylate-cAMP system.
 ...
PMID:Control of hepatic glycogen metabolism in the rhesus monkey: effect of glucose, insulin, and glucagon administration. 16 92

Expression of the glycogenolytic action of glucagon in liver requires ATP for cAMP formation and for several subsequent phosphorylation reactions. To assess the extent to which ATP availability is rate-limiting to this hormonal action, responses to glucagon of intact liver and of liver with marked reductions in ATP content induced by ethionine was examined in female Wistar rats in vivo and in vitro. Compared to values in quick-frozen liver samples from control rats, basal hepatic ATP was 75% lower and cAMP, two fold higher in rats treated with ethionine. Activation of glycogen phosphorylase and inactivation of glycogen synthetase, phosphorylation reactions which require ATP and are initiated by cAMP, were also evident in basal liver samples from ethionine-treated rats. These hepatic alterations were associated with portal glucose and insulin levels which were significantly lower and portal glucagon levels which were four fold higher than values in controls. In ethionine-treated rats, glucose infusion decreased hepatic cAMP content and phosphorylase activity and increased synthetase activity. This and other observation suggested that the higher cAMP and the altered enzyme activities seen in vivo after ethionine administration were mediated by the hyperglucagonemia and/or by other endogenous glycogenolytic stimuli, and accordingly implied that liver remained responsive to such stimuli despite reduced ATP. Pharmacologic doses of exogenous glucagon clearly increased cAMP in vivo and in vitro in livers with decreased ATP. However, the lower ATP of liver exposed to ethionine was associated with a significantly blunted cAMP response to maximal glucagon stimulation. By contrast, alterations in phosphorylase and synthetase activities were not similarly blunted, suggesting that the smaller increases in cAMP seen in liver with reduced ATP content were adequate for the expression of these actions of the hormone. It is concluded that the actions of glucagon to increase cAMP and to activate phosphorylase and inactivate synthetase are not abolished by marked reductions in hepatic APT.
 ...
PMID:Effects of reduced ATP concent on hepatic responses to glucagon. 17 76

In liver cells isolated from fed female rats, glucagon (290nM) increased adenosine 3':5'-monophosphate (cyclic AMP) content and decreased cyclic AMP binding 30 s after addition of hormones. Both returned to control values after 10 min. Glucagon also stimulated cyclic AMP-independent protein kinase activity at 30 s and decreased protein kinase activity assayed in the presence of 2 muM cyclic AMP at 1 min. Glucagon increased the levels of glycogen phosphorylase a, but there was no change in total glycogen phosphorylase activity. Glucagon increased glycogen phosphorylase a at concentrations considerably less than those required to affect cyclic AMP and protein kinase. The phosphodiesterase inhibitor, 1-methyl-3-isobutyl xanthine, potentiated the action of glucagon on all variables, but did not increase the maximuM activation of glycogen phosphorylase. Epinephrine (1muM) decreased cyclic AMP binding and increased glycogen phosphorylase a after a 1-min incubation with cells. Although 0.1 muM epinephrine stimulated phosphorylase a, a concentration of 10 muM was required to increase protein kinase activity. 1-Methyl-3-isobutyl xanthine (0.1 mM) potentiated the action of epinephrine on cyclic AMP and protein kinase. (-)-Propranolol (10muM) completely abolished the changes in cyclic AMP binding and protein kinase due to epinephrine (1muM) in the presence of 0.1mM 1-methyl-3-isobutyl xanthine, yet inhibited the increase in phosphorylase a by only 14 per cent. Phenylephrine (0.1muM) increased glycogen phosphorylase a, although concentrations as great as 10 muM failed to affect cyclic AMP binding or protein kinase in the absence of phosphodiesterase inhibitor. Isoproterenol (0.1muM) stimulated phosphorylase and decreased cyclic AMP binding, but only a concentration of 10muM increased protein kinase. 1-Methyl-3-isobutyl xanthine potentiated the action of isoproterenol on cyclic AMP binding and protein kinase, and propranolol reduced the augmentation of glucose release and glycogen phosphorylase activity due to isoproterenol. These data indicate that both alpha- and beta-adrenergic agents are capable of stimulating glycogenolysis and glycogen phosphorylase a in isolated rat liver cells. Low concentrations of glucagon and beta-adrenergic agonists stimulate glycogen phosphorylase without any detectable increase in cyclic AMP or protein kinase activity. The effects of alpha-adrenergic agents appear to be completely independent of changes in cyclic AMP protein kinase activity.
 ...
PMID:Activation of protein kinase and glycogen phosphorylase in isolated rat liver cells by glucagon and catecholamines. 18 18

We have studied the mode of action of three hormones (angiotensin, vasopressin and phenylephrine, an alpha-adrenergic agent) which promote liver glycogenolysis in a cyclic AMP-independent way, in comparison with that of glucagon, which is known to act essentially via cyclic AMP. The following observations were made using isolated rat hepatocytes: (a) In the normal Krebs-Henseleit bicarbonate medium, the hormones activated glycogen phosphorylase (EC 2.4.1.1) to about the same degree. In contrast to glucagon, the cyclic AMP-independent hormones did not activate either protein kinase (EC 2.7.1.37) or phosphorylase b kinase (EC 2.7.1.38). (b) The absence of Ca2+ from the incubation medium prevented the activation of glycogen phosphorylase by the cyclic AMP-independent agents and slowed down that induced by glucagon. (c) The ionophore A 23187 produced the same degree of activation of glycogen phosphorylase, provided that Ca2+ was present in the incubation medium. (d) Glucagon, cyclic AMP and three cyclic AMP-dependent hormones caused an enhanced uptake of 45Ca; it was verified that concentrations of angiotensin and of vasopressin known to occur in haemorrhagic conditions were able to produce phosphorylase activation and stimulate 45Ca uptake. (e) Appropriate antagonists (i.e. phentolamine against phenylephrine and an angiotensin analogue against angiotensin) prevented both the enhanced 45Ca uptake and the phosphorylase activation. We interpret our data in favour of a role of calcium (1) as the second messenger in liver for the three cyclic AMP-independent glycogenolytic hormones and (2) as an additional messenger for glucagon which, via cyclic AMP, will make calcium available to the cytoplasm either from extracellular or from intracellular pools. The target enzyme for Ca2+ is most probably phosphorylase b kinase.
 ...
PMID:On the role of calcium as second messenger in liver for the hormonally induced activation of glycogen phosphorylase. 18 44

Hepatocytes isolated from the livers of fed rats were used for a comparative study of the effects of phenylephrine, vasopressin and glucagon on gluconeogenesis and on enzymes of glycogen metabolism. When hepatocytes were incubated in the presence of Ca(2+), phenylephrine stimulated gluconeogenesis from pyruvate less than did glucagon, but, in contrast with this hormone, it did not affect the activities of protein kinase and pyruvate kinase, nor the concentration of phosphoenolpyruvate, and it did not decrease the release of (3)H(2)O from [6-(3)H]glucose. The effects of vasopressin were similar to those of phenylephrine. Gluconeogenesis from fructose was also stimulated by phenylephrine and, more markedly, by glucagon at the expense of the conversion of fructose into lactate. Insulin was able to antagonize the stimulatory effect of phenylephrine on gluconeogenesis from pyruvate. When Ca(2+) was removed from the incubation medium, phenylephrine still stimulated gluconeogenesis from pyruvate, but it also caused an activation of protein kinase and an inactivation of pyruvate kinase; accordingly, the concentration of phosphoenolpyruvate was increased, and, in contrast, vasopressin had no effect on all these parameters. The property of phenylephrine to cause the activation of glycogen phosphorylase was decreased by glucose or by the absence of Ca(2+); it was abolished when these two conditions were combined. Glycogen synthase was inactivated by phenylephrine in the presence or the absence of Ca(2+), although presumably by different mechanisms.
 ...
PMID:Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon. 74 52

In rats exposed to 400 revolutions (during 6 min and 40 sec) in rotating Noble-Collip drums essentially the same increase of the active form of hepatic glycogen phosphorylase as in animals studied 6 min and 40 sec after epinephrine (50 microgram/kg) or glucagon (100 microgram/kg), both i.v., was observed. However, in rats injured daily for 6 days, on day 7 this enzyme response was substantially blunted.
 ...
PMID:The increase of the active form of hepatic glycogen phosphorylase in stressed rats. 92 34

Metabolic effects of vasopressin, glucagan and adrenalin were compared, in intact rats, especially in regard to time courses of effects. Hyperglycaemia was transient in response to vasopressin, prolonged following adrenalin, and, suprisingly, was not discernible after glucagon, except in response to a very large dose. Vasopressin decreased and adrenalin increased, the plasma free fatty acid concentration; both hormones decreased the triacylglycerol level. Muscle glycogen concentrations, measured in heart, diaphragm and skeletal muscle, exhibited small changes, with complex time courses, following hormone administration. Vasopressin brought about a rapid but transient activation of heaptic glycogen phosphorylase which resembled that due to adrenalin. The activation by glucagon of phosphorylase was greater and more prolonged, despite the absence of hyperglycaemia. In response to vasopressin, there was in increase in plasma insulin. Incorporation of 14C from [14C]glucose into glycogen or fatty acids was not influenced by vasopressin. Taken together, these results may be explained by rapid metabolic action of vasopressin on hepatic glycogenolysis, whereas adrenalin has multiple prolonged actions.
 ...
PMID:Metabolic actions of vasopressin, glucagon and adrenalin in the intact rat. 118

In rat hepatocytes, molybdate and tungstate inactivate glycogen synthase by a mechanism independent of Ca2+ and activate glycogen phosphorylase by a Ca(2+)-dependent mechanism. On the other hand, both molybdate and tungstate increase fructose 2,6-bisphosphate levels and counteract the decrease in this metabolite induced by glucagon. These effectors do not directly modify 6-phosphofructo-2-kinase activity, even though they partially counteract the inactivation of this enzyme induced by glucagon. These effects are related to an increase on the glycolytic flux, as indicated by the increase in L-lactate and CO2 production and the decrease in glucose 6-phosphate levels in the presence of glucose. All these effects are similar to those previously reported for vanadate, although molybdate and tungstate are less effective than vanadate. These results could indicate that molybdate, tungstate and vanadate act on glucose metabolism in isolated hepatocytes by a similar mechanism of action.
 ...
PMID:Molybdate and tungstate act like vanadate on glucose metabolism in isolated hepatocytes. 131 28

Hepatocytes isolated from the liver of rats after a necrotizing dose of thioacetamide (6.6 mmol/kg) were used to study the postnecrotic process of liver regeneration. Flow cytometry analysis revealed populations of dedifferentiated hepatocytes exhibiting physical properties (size and fluorescence emission at 530 nm) similar to those found in fetal (22 days old) liver cells. The percentage of these cells increased progressively from 24 to 48 and 72 hr after thioacetamide administration. In primary cultures of hepatocytes the effects of phorbol 12-myristate 13-acetate, bombesin and insulin were investigated on the 6-phosphofructo 2-kinase/fructose 2,6 bisphosphate system. Bombesin and insulin stimulated 6-phosphofructo 2-kinase activity and fructose 2,6-bisphosphate content both in control and in thioacetamide-treated hepatocytes. However, phorbol 12-myristate 13-acetate stimulated 6-phosphofructo 2-kinase activity and increased fructose 2,6-bisphosphate concentration in thioacetamide-treated liver cells, whereas no similar response was found in hepatocytes from control rats. The response of postnecrotic thioacetamide-treated hepatocytes to phorbol 12-myristate 13-acetate was similar to that obtained from 22-day-old fetal liver cells, which reveals that different methods might control fructose 2,6-bisphosphate content and therefore the mechanisms of glycolysis and gluconeogenesis at this regulatory step. The lack of response to glucagon of glycogen phosphorylase a and 6-phosphofructo 2-kinase from thioacetamide-treated hepatocytes may indicate that the expression of specific enzymes of carbohydrate metabolism undergoes transitions to less-differentiated isoenzymatic forms. Moreover, the isoenzyme pattern of hexokinases elicits a complete disturbance in glucokinase and hexokinases activities.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Isoenzymes of carbohydrate metabolism in primary cultures of hepatocytes from thioacetamide-induced rat liver necrosis: responses to growth factors. 131 52


1 2 3 4 5 6 7 8 9 10 Next >>