Role of Ca2+ in alloxan-induced pancreatic beta-cell damage

Abstract

Pretreatment of rats with verapamil, a Ca(2+)-antagonist, completely prevented alloxan-induced hyperglycemia. Verapamil also abolished the inhibition of insulin secretion by alloxan and H2O2 in isolated rat pancreatic islets. H2O2 generation from alloxan was not affected by verapamil, but alloxan- and H2O2-induced DNA strand breaks were completely prevented. Treatment of beta-cells with alloxan and H2O2 caused elevation of cytosolic free Ca2+, and this increase of Ca2+ was also abolished by verapamil. These results suggest that alloxan-derived oxygen radicals may disturb intracellular Ca2+ homeostasis by increasing Ca2+ influx, which results in secondary reactions ultimately leading to DNA strand breaks and cytotoxicity of beta-cells.