The effect of probucol on the development of non-insulin dependent diabetes mellitus in Otsuka Long Evans Tokushima Fatty (OLETF) rats.

The effect of probucol which acts as a scavenger of free radicals, on preventing the development of non-insulin dependent diabetes mellitus (NIDDM) in a model rat (Otsuka Long Evans Tokushima Fatty [OLETF]) was examined. Sixteen male OLETF rats aged 5 weeks were divided into two groups. One group were fed standard laboratory chow and the other group were fed the chow containing 1% probucol. At 12, 16, 24 weeks of age, an oral glucose tolerance test (OGTT) was performed. At 24 weeks of age, the cumulative incidences of diabetes mellitus in both groups were 100%. After two weeks, insulin-mediated glucose uptake was measured using a euglycemic clamp technique. There was no significant difference in glucose infusion rates between both groups. At the end of the experiment, plasma lipid concentrations were measured. The serum total cholesterol levels were significantly lower in rats fed probucol containing chow (66.3 +/- 3.7 mg/dl) than those of rats fed standard laboratory chow (78 +/- 6.4 mg/dl). On the other hand, the serum triglyceride level were not significantly different between them. Histological studies on the pancreas of both groups showed enlarged fibrotic islets and mononuclear cell infiltration in the periinsular area, though to a modest extent. These results demonstrated that probucol was not effective in preventing the development of NIDDM in this model animal. Considering these data, inflammatory destruction of pancreatic beta cells by free radical may not be involved in the development of NIDDM.