Parallel Inhibition of Islet Glucokinase and Glucose-Stimulated Insulin Secretion by Either Alloxan or Ninhydrin

Treatment of pancreatic islets with alloxan or ninhydrin at concentrations that induced the inhibition of glucokinase activity similarly inhibited glucose-stimulated insulin secretion. Alloxan- or ninhydrin-induced inhibition of glucokinase activity was blocked by the presence of hexoses, which also protected against the inhibitory effect of each drug on insulin secretion. The protective effect of D-glucose against the inhibition of glucokinase activity by alloxan or ninhydrin showed α-anomeric preference, which was similarly observed in the protection by the sugar against the inhibition of insulin secretion. These results suggest that the inhibition of glucose-stimulated insulin secretion by treatment of pancreatic islets with alloxan or ninhydrin is due to the inhibition of glucokinase.