Insulin release from mouse islets. Effect of glucose and hormones on adenylate cyclase.
The adenylate cyclase system of normal mouse islets was characterized. The pH optimum of the system was 7.6. The enzyme preparation contained particulate phosphodiesterase activity. This could be removed by treatment with 0.4% (v/v) Triton X-100 or inhibited by 8mm-theophylline in the presence of 2mm-cyclic AMP (adenosine 3':5'-cyclic monophosphate). ATP at 0.32mm produced one-half maximal enzyme activity. The enzyme was stimulated in the presence of F(-) and strongly inhibited by Ca(2+). The isolated enzyme retained hormonal sensitivity and was stimulated by glucagon, pancreozymin and secretin at physiological concentrations. Glucose at 17mm, 8mm and 2mm had no direct effect on the activity of the enzyme; neither did galactose at the same concentrations. Groups of islets incubated in 17mm- or 2mm-glucose for 5 or 15min and then homogenized and assayed for adenylate cyclase activity showed no differences in adenylate cyclase activity. The results suggest that the mechanism of glucose-mediated insulin release is not via the adenylate cyclase system. Hormones, however, could mediate insulin secretion via their effects on the adenylate cyclase system.
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D005690:Galactose / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D010727:Phosphoric Diester Hydrolases; D012633:Secretin / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D007328:Insulin; D013501:Surface-Active Agents; D012633:Secretin; D005934:Glucagon; D002766:Cholecystokinin; D013806:Theophylline; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D005947:Glucose; D005459:Fluorides; D002118:Calcium; D005690:Galactose