Impaired insulin release after exposure of pancreatic islets to autooxidizing dihydroxyfumarate

Autooxidizing dihydroxyfumarate (DHF) is a known generator of superoxide anions and by hydroxyl free radicals. Isolated rat pancreatic islets were exposed for 5 min to 0.4 mg/ml DHF in an oxygenated buffer solution. As a result of this exposure, the islets exhibited a 60% reduction in glucose-stimulated insulin release. The presence of superoxide dismutase, catalase, or diethylenetriaminepentaacetic acid, a metal chelator, during the exposure period protected the islets from the effects of autooxidizing DHF. This suggests that superoxide anions, hydrogen peroxide, and, ultimately, hydroxyl free radicals play a role in the insulin inhibitory effects caused by DHF exposure. Glucose (5 mg/ml), but not galactose, was also capable of protecting islets from DHF. The effects of DHF exposure on isolated islets appear to be similar to those previously reported for alloxan and lend support to the concept that hydroxyl free radicals generated during the oxidation of certain compounds can alter endocrine cell function.