Mechanisms of [Ca²⁺]_i elevation by H₂O₂ in islets of rats

Activity of reactive oxygen species is elevated in diabetes mellitus and has been implicated in the destruction of cellular components. The toxic effect of reactive oxygen species was investigated by testing the effect of H₂O₂ on [Ca²⁺]_i in isolated islets of Langehans. H₂O₂ increased [Ca²⁺]_i in a dose-dependent manner, which was irreversible at high concentrations. The maximum effect of H₂O₂ on [Ca²⁺]_i was larger than those of KC1, glucose, ATP, carbachol and endothelin-1. The effect of H₂O₂ was only partially attenuated by removal of external Ca²⁺ and by the in-organic Ca²⁺ channel blocker nickel, but was not blocked by voltage-dependent or -independent Ca²⁺ channel blockers nimodipine, nicardipine, SK&F 96365, econazole and lanthanum. H₂O₂, disrupted [Ca²⁺]_i homeostasis in islets by affecting both release and influx of Ca²⁺ and causing dysfunction of Ca²⁺ clearance systems and may contribute to the pathological process of diabetes.