Abstract

BACKGROUND
It has been hypothesized that reactive oxygen species (ROS) are involved in the progression of beta cell dysfunction in both type 1 and type 2 diabetes mellitus. On the other hand, recent evidence suggests that ROS might be an integral component of intracellular signaling. This study was undertaken to examine effects of hydrogen peroxide (H2O2) on insulin secretion by various secretagogues in isolated rat pancreatic islets. METHODS: Pancreatic islets from normal Sprague-Dawley rats were isolated by intraductal injection of collagenase and Ficoll-gradient centrifugation. Isolated islets were treated with H2O2 directly added to the culture media or continuously generated by glucose-glucose oxidase system for 24 hours. Insulin secretion stimulated by glucose, arginine, and KCl was measured by radioimmunoassay. RESULTS: Basal insulin secretion was increased after treatment with H2O2. Treatment with low concentration of H2O2 stimulated insulin secretion in response to 27 mM glucose. In contrast, insulin secretion stimulated by 27 mM glucose was significantly decreased after treatment with high concentrations of H2O2. Arginine- stimulated insulin secretion was increased by both low- and high concentrations of H2O2. Insulin secretion stimulated by KCl was not affected by treatment with H2O2. CONCLUSION: These results suggest that the effect of H2O2 is diverse according to its concentration and different insulin secretagogues. In particular, H2O2 has a dual action on glucose-induced insulin secretion. At low concentration, H2O2 can stimulate insulin secretion probably by acting on signaling pathway of stimulus- secretion coupling. In contrast, high concentrations of H2O2 impairs glucose- induced insulin secretion, probably by acting as an oxidative stress.

• Keywords: Insulin secretion;Hydrogen peroxide;Rat pancreatic islets;Stimulus-secretion coupling;Oxidative stress;