Excessively high glucose concentrations have been shown to damage tissues through stimulation of mitochondrial superoxide generation. This effect has therefore been considered as a potential cause for dysfunction and death of pancreatic beta cells in diabetes. We have examined whether the rate of glucose metabolism in isolated rat beta cells is correlated with their formation of oxygen radicals. It was found that high rates of glucose metabolism did not stimulate the formation of superoxide and H(2)O(2) but suppressed it. The higher rates of superoxide production in beta cells with lower mitochondrial metabolic activity contributed to the susceptibility of these cells to apoptosis.