Effects of alloxan on the islets of Langerhans. Possible mechanisms of diabetogenic action.

To study some possible mechanisms responsible for the diabetogenic action of alloxan on the islets of Langerhans, islets isolated from normal mice were exposed to the drug at 4 degrees C. The low temperature employed during alloxan exposure minimized the degradation of the drug. Incubations performed at 37 degrees C after alloxan treatment of the islets in the cold showed that the drug had no effect on islet glucose utilization, whereas both islet glucose and leucine oxidation were inhibited. However, alloxan did not affect the islet activity of the plasma membrane bound enzyme adenylate cyclase (E.C. 4.6.1.1). From these and previous results it is concluded that the B-cytotoxicity of alloxan reflects an interaction with intracellular sites involved in the oxidative metabolism of the B-cell rather than with B-cell plasma membrane components. Furthermore, it was found that glucose, but not leucine or pyruvate, could protect against the inhibition of islet glucose oxidation. These findings could suggest that the B-cytotoxic action of the drug is prevented exclusively by hexoses.