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

Pretreatment of rats with verapamil, a Ca²⁺-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 β-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 β-cells.