DIFFERENTIAL METABOLIC REQUIREMENT FOR INITIATION AND AUGMENTATION OF INSULIN 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)]glucose) were determined in pancreatic islets from 96-h fasted rats at 37 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 from 96-h fasted rats and those from fed rats incubated at 22 degrees C, we could not demonstrate significant insulin release in response to high glucose concentrations of up to 16.7 mmol/l. However, 16.7 mmol/l glucose clearly augmented insulin release caused by a depolarizing concentration (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 cells were suppressed by 96-h fasting of the rats or by lowering the incubation temperature to 22 degrees C, and depolarization with K+ at 50 mmol/l did not at all augment glucose utilization and oxidation by the islets. Thus we conclude that reduction of glucose metabolism in islets from fasted rats and in those incubated at low temperature eliminated initiation, but not augmentation, of insulin release by 16.7 mmol/l glucose. The data indicate that the metabolic threshold for the initiation of insulin release is significantly higher than it is for the augmentation of release by glucose.