Effects of alloxan on the islets of Langerhans: stimulation and inhibition of cyclic AMP production.

Alloxan exerts a selective impairment of the insulin-producing B-cells of the islets of Langerhans, which may result in diabetes mellitus. The effects of alloxan on cyclic AMP metabolism in isolated mouse islets of Langerhans were investigated. Alloxan caused an immediate increase in islet content of cyclic AMP, whereas a subsequent glucose-stimulated increase of islet cyclic AMP content was inhibited in alloxan-exposed islets. No corresponding effects of the drug were, however, found on either islet adenylate cyclase or cyclic AMP phosphodiesterase activities in broken cell preparations. It appears unlikely that there is a direct interaction between alloxan and the enzyme molecules leading to irreversible changes. Alloxan may rather affect some metabolic factor essential for optimal enzyme function. The inhibition of glucose-stimulated increase in islet ATP content and adenylate energy charge in alloxan-treated islets suggests that such a factor might be dependent on intact ATP generation.