OXIDATIVE STRESS CAUSES DEPOLARIZATION AND CALCIUM-UPTAKE IN THE RAT INSULINOMA CELL RINM5F

Generation of free radicals and oxidative stress play a role in the de velopment of islet dysfunction in diabetes. These mechanisms are known to affect membrane potential and cytosolic calcium in other cell type s. The effect of oxidative stress, caused by tert-butyl-hydroperoxide (BuOOH), was therefore studied with respect to the redox ratio of glut athione, membrane potential, cytosolic calcium and insulin release in the insulin-secreting RINm5F cell. In RINm5F cells BuOOH decreased the redox ratio of glutathione and caused depolarization. This was associ ated with an increase in cytosolic calcium and insulin secretion. The effects of BuOOH on cytosolic calcium and insulin release were abolish ed in the absence of extracellular calcium and decreased by the calciu m channel blocker verapamil. Our data suggest that in RINm5F cells oxi dative stress causes insulin release by depolarization and subsequent calcium entry through voltage-dependent calcium channels.