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

Abstract

The inhibitory effect of hydrogen peroxide (H 2O 2) 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 H 2O 2 (5-10 μmol/L) on glucose metabolism, intracellular calcium ([Ca 2+] i) oscillations, and dynamic insulin secretion in rat pancreatic islets were investigated. Low concentrations of H 2O 2 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 H 2O 2. Glucose oxidation and the amplitude of [Ca 2+] i oscillations were dose-dependently suppressed by H 2O 2. These findings indicate that low concentrations of H 2O 2 reduce insulin secretion in the presence of high glucose levels via inhibition of glucose metabolism and consequent impairment in [Ca 2+] i handling.