Low doses of hydrogen peroxide impair glucose-stimulated insulin secretion via inhibition of glucose metabolism and intracellular calcium oscillations

The inhibitory effect of hydrogen peroxide (H2O2) on glucose-stimulated insulin secretion was previously reported. However, the precise mechanism involved was not systematically investigated. In this study, the effects of low concentrations of H2O2 (5-10 μmol/L) on glucose metabolism, intracellular calcium ([Ca2+]i) oscillations, and dynamic insulin secretion in rat pancreatic islets were investigated. Low concentrations of H2O2 impaired insulin secretion in the presence of high glucose levels (16.7 mmol/L). This phenomenon was observed already after 2 minutes of exposure to H2O2. Glucose oxidation and the amplitude of [Ca2+]i oscillations were dose-dependently suppressed by H2O2. These findings indicate that low concentrations of H2O2 reduce insulin secretion in the presence of high glucose levels via inhibition of glucose metabolism and consequent impairment in [Ca2+]i handling.