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)

Previous studies have demonstrated that prostaglandins stimulate glucagon secretion in vitro and in vivo. The present work was aimed at investigating the influence of two inhibitors of prostaglandin synthesis, isopropyl-2 nicotinoyl-3 indole (L8027) and indomethacin, on basal and arginine- or noradrenaline-stimulated glucagon release from isolated guinea-pig islets incubated in the absence of glucose. L8027 (10(-4) and 10(-5) mol/l) did not alter basal glucagon release, blocked almost completely the glucagon response to arginine (10(-2) mol/l), had no effect on the glucagon release induced by noradrenaline (10(-4) mol/l), but reduced the stimulatory effect of a lower concentration of noradrenaline (5.10(-7) mol/l). The kinetic study of this inhibitory effect demonstrated that (1) it necessitates preincubation of the islets with L8027 for 30 minutes before the addition of arginine, (2) after a short preincubation period (30 minutes) in the presence of L8027, removal of the inhibitor at the time of arginine stimulation resulted in enhanced glucagon response, (3) on the contrary, after a prolonged incubation period (75 min) with arginine and L8027, the inhibitory effect remained transiently detectable after removal of L8027. Indomethacin similarly blocked arginine- and noradrenaline-induced glucagon secretion. These results suggest that an intra-insular synthesis of prostaglandins is involved in the A cell response to arginine and noradrenaline.
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PMID:Possible role of endogenous prostaglandins in glucagon secretion by isolated guinea-pig islets. 36 55

The involvement of endogenous prostaglandins (PGs) in pancreatic endocrine and exocrine secretion was investigated, using the isolated and perfused dog pancreas. Spontaneous production of both PGE2 and 6-keto-PGF1 alpha was recorded in venous effluent. Prostaglandin production increased following stimulation with both 10 x 10(-11) and 20 x 10(-11) mol of CCK-8, but was not affected by a 5 x 10(-11) mol infusion. Insulin, glucagon, and amylase release was stimulated by 10 x 10(-11) mol of CCK-8. Indomethacin pretreatment with 10 mg/kg totally abolished endogenous PG production, but failed to suppress an insulin and glucagon response. On the other hand, an amylase response was accelerated by indomethacin pretreatment. Although low dose CCK-8 failed to stimulate endogenous prostaglandin production, a brisk exocrine secretion was not suppressed by indomethacin pretreatment. From the above results, we conclude that endogenous PGs do not appear to play an important role in pancreatic endocrine and exocrine secretion, but might have a cytoprotective effect on the pancreatic acinar cells damaged by CCK-8.
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PMID:Involvement of endogenous prostaglandins in pancreatic endocrine and exocrine secretion in dog pancreas. 247

Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p less than 0.01 vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5 +/- 4 microU/ml to 88 +/- 11 microU/ml, p less than 0.001) and restored to normal the reduced glucose tolerance (KG from 1.10 +/- 0.1% min-1 to 2.04 +/- 0.19% min-1). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.
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PMID:Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts. 331 57

We previously demonstrated that treatment with indomethacin in vivo significantly blunted the glucagon-induced glycemic response in the rat. This prostaglandin synthetase (cyclo-oxygenase) inhibitor also accentuated the evanescent effect of glucagon on hepatic glucose output in the intact, anesthetized rat. In this report, we present evidence that impairment of glucagon action in the rat liver by indomethacin is mediated through its inhibitory effect on both cAMP-dependent and cAMP-independent hepatic protein kinase. Indomethacin treatment did not have a measurable effect on any of the other components of the glucagon transducer system. Furthermore, infusion with glucagon for two hours that maintained plasma glucagon values at high physiological levels significantly reduced hepatic cAMP-dependent protein kinase activity without altering its Km. Glucagon infusion also down-regulated its own hepatic receptors and glucagon-stimulated cAMP production; prostaglandin E1-stimulated cAMP production was not affected. We concluded that prostaglandins may play a role in the regulation of hepatic protein kinases involved in the glucagon-stimulated glycogenolytic response and that glucagon-induced down-regulation extends at least to the hepatic protein kinases. However, a direct effect of indomethacin or protein kinase and the adenylate cyclase complex cannot be ruled out.
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PMID:Modulation of hepatic protein kinase activity by indomethacin. 608 43

The involvement of prostaglandins in the effects of arachidonic acid (20:4n-6) on insulin and glucagon release was investigated, using the isolated, perfused rat pancreas model. 20:4n-6, the substrate for dienoic prostaglandins, or 20:3n-3, a fatty acid that cannot be metabolized to prostaglandins were perfused over 55 min. 20: 4n-6 evoked triphasic insulin release: early and late phase during, and "off-response" following the perfusion. With 20:3n-3 the early phase of insulin release was 57% of that with 20:4n-6. 20:4n-6 stimulated only an early phase release of glucagon; 20:3n-3 had no effect. Indomethacin (10 microM, a cyclooxygenase inhibitor) inhibited by 50% the early phase of insulin and glucagon release induced by 20:4n-6, but did not modify insulin release during the early phase with 20:3n-3, or the late phase or off-response with either 20:4n-6 or 20:3n-3. We conclude that 1) the early phase release of insulin and glucagon which occurs with arachidonic acid is due in part to pancreatic biosynthesis of prostaglandins; and 2) in the other phases of insulin release evoked by the fatty acids, alternate "nonspecific" mechanisms may be involved.
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PMID:Arachidonic acid induced release of insulin and glucagon: role of endogenous prostaglandins in pancreatic hormone secretion. 643 Jul 28

We have investigated the influence of a single oral administration of indomethacin on blood glucose, plasma free fatty acids (FFA), alpha-amino-nitrogen, insulin and glucagon concentrations in young healthy subjects. Two groups of 6 subjects were studied, the first received a standardized 500 kcal mixed meal without any previous drug administration (controls) whereas the second group received 50 mg indomethacin 2 h before ingesting an identical meal. Plasma indomethacin concentration reached its maximum (2.36 +/- 0.36 micro g/ml) 15 min after administration and declined to 0.45 +/- 0.04 micro g/ml after 2 h. Indomethacin ingestion was followed by a significant increase in blood glucose and plasma FFA reaching their maximum value at 45 min and returning to basal levels at 120 min. No simultaneous changes in plasma alpha-amino-nitrogen, insulin or glucagon levels were detected during this period. The meal was followed by a rise in blood glucose and plasma insulin as well as by a decrease in plasma FFA concentration. No significant differences were detected between the controls and the subjects receiving indomethacin. In controls, the meal was followed by a rise in plasma alpha-amino-nitrogen and a modest although significant increase in glucagon levels. In indomethacin-treated subjects, the increment of alpha-amino-nitrogen was less marked and the increase in plasma glucagon was not observed. Thus, indomethacin by itself can exert several metabolic effects; however, it does not deteriorate the blood glucose or insulin profile after a regular meal. The present work is the first to demonstrate that an inhibitor of prostaglandin synthesis inhibits the plasma glucagon rise occurring after a physiological stimulus such as a normal meal. On the basis of previous in vitro experiments, we suggest that this effect results from an inhibition of glucagon secretion by the PG synthesis inhibitor.
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PMID:Effect of indomethacin on the metabolic and hormonal response to a standardized breakfast in normal subjects. 702 90