Beneficial effects of antioxidants in diabetes - Possible protection of pancreatic beta-cells against glucose toxicity

Oxidative stress is produced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. The aim of this s tudy was to examine the involvement of oxidative stress in the progression of pancreatic beta-cell dysfunction in type 2 diabetes and to evaluate the potential usefulness of antioxidants in the treatment of type 2 diabetes. W e used diabetic C57BL/KsJ-db/db mice, in whom antioxidant treatment (N-acet yl-L-cysteine [NAC], vitamins C plus E, or both) was started at 6 weeks of age; its effects mere evaluated at 10 and 16 weeks of age. According to an intraperitoneal glucose tolerance test, the treatment with NAC retained glu cose-stimulated insulin secretion and moderately decreased blood glucose le vels. Vitamins C and E were not effective when used alone but slightly effe ctive when used in combination with NAC. No effect on insulin secretion was observed when the same set of antioxidants was given to nondiabetic contro l mice. Histologic analyses of the pancreases revealed that the beta-cell m ass was significantly larger in the diabetic mice treated with the antioxid ants than in the untreated mice. As a possible cause, the antioxidant treat ment suppressed apoptosis in beta-cells without changing the rate of beta-c ell proliferation, supporting the hypothesis that in chronic hyperglycemia, apoptosis induced by oxidative stress causes reduction of beta-cell mass. The antioxidant treatment also preserved the amounts of insulin content and insulin mRNA, making the extent of insulin degranulation less evident. Fur thermore, expression of pancreatic and duodenal homeobox factor-1 (PDX-1), a beta-cell-specific transcription factor, was more clearly visible in the nuclei of islet cells after the antioxidant treatment. In conclusion, our o bservations indicate that antioxidant treatment can exert beneficial effect s in diabetes, with preservation of in vivo beta-cell function. This findin g suggests a potential usefulness of antioxidants for treating diabetes and provides further support for the implication of oxidative stress in beta-c ell dysfunction in diabetes.