DIFFERENTIAL METABOLIC REQUIREMENT FOR INITIATION AND AUGMENTATION OFINSULIN RELEASE BY GLUCOSE - A STUDY WITH RAT PANCREATIC-ISLETS

Insulin release, glucose utilization ((H2O)-H-3 formation from [5-H-3] glucose), and glucose oxidation ((CO2)-C-14 formation from [C-14(U)]gl ucose) were determined in pancreatic islets from 96-h fasted rats at 3 7 degrees C and those from fed rats at 22 degrees C, using the islets from fed rats incubated at 37 degrees C as controls. In the islets fro m 96-h fasted rats and those from fed rats incubated at 22 degrees C, we could not demonstrate significant insulin release in response to hi gh glucose concentrations of up to 16.7 mmol/l. However, 16.7 mmol/l g lucose clearly augmented insulin release caused by a depolarizing conc entration (50 mmol/l) of K+ in these islets: i.e. 16.7 mmol/l glucose plus 50 mmol/l K+ produced significantly greater insulin release than 50 mmol/l K+ alone. Glucose utilization and oxidation by the islet cel ls were suppressed by 96-h fasting of the rats or by lowering the incu bation temperature to 22 degrees C, and depolarization with K+ at 50 m mol/l did not at all augment glucose utilization and oxidation by the islets. Thus we conclude that reduction of glucose metabolism in islet s from fasted rats and in those incubated at low temperature eliminate d initiation, but not augmentation, of insulin release by 16.7 mmol/l glucose. The data indicate that the metabolic threshold for the initia tion of insulin release is significantly higher than it is for the aug mentation of release by glucose.