Effects of alloxan on glucose-stimulated insulin secretion, glucose metabolism, and cyclic adenosine 3', 5'-monophosphate levels in rat isolated islets of langerhans.
Insulin secretion was stimulated and cyclic adenosine 3', 5'-monophosphate (cAMP) levels were elevated in isolated rat islets by 27.5 mmol/l glucose. Alloxan caused a dose-dependent decrease in both variables with complete obliteration of insulin release at a concentration of 1.25 mmol/l. D-glucose, in the presence or absence of extracellular calcium, or 3-0-methyl-D-glucose (both at 27.5 mmol/l) protected completely against the effects of alloxan on both glucose-induced insulin release and cAMP Levels. 3-0-Methylglucose did not stimulate insulin secretion or elevate cAMP and did not interfere with glucose-stimulated secretion or elevation of cAMP. When glucose-stimulated insulin release was abolished by alloxan, the metabolism of glucose, determined by the rate of 3H2O formation from [5-3H] glucose, was depressed by 20%. It is concluded that alloxan altered the adenylate cyclase system such that it could no longer be stimulated by glucose. Glucose-stimulated insulin secretion or elevation of cAMP did not appear essential for glucose to protect against alloxan. Protection by 3-0-methylglucose did not appear to be mediated through an alteration of cAMP metabolism. Alloxan did not inhibit glucose-induced insulin secretion by grossly altering glycolysis.
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D008757:Methylglucosides / Q000494:pharmacology; D051381:Rats
D007328:Insulin; D008757:Methylglucosides; D000496:Alloxan; D000242:Cyclic AMP; D005947:Glucose; D002118:Calcium