PANCREATIC ANTIOXIDANT ENZYME-ACTIVITY IN NORMOGLYCEMIC DIABETIC PRONE BB RATS

Free radicals have been implicated in beta-cell destruction. Pancreati c antioxidant enzymatic defenses provide significant endogenous protec tion from these highly cytotoxic effector molecules. In our colony of BB rats, the reliability of peripheral blood lymphocyte count (PBLC) a s a predictor of diabetes onset was assessed in 99 male and 110 female BB rats. In rats with a PBLC <4,200 mm(3), 90% of mates and 86% of fe males developed diabetes by 120 days of age and are designated ''lymph openic'' or BBL. Rats with a PBLC >4,200 mm(3) have a much lower incid ence of insulin-dependent diabetes mellitus (IDDM) and are designated ''nonlymphopenic'' or BBNL. In separate cohorts of normoglycemic (pred iabetic) BBL rats (high risk for developing diabetes) and BBNL rats (l ow risk for developing diabetes), the activities of pancreatic cytosol ic antioxidant enzymes, copper-zinc superoxide dismutase (CuZnSOD), ca talase (CAT), and glutathione peroxidase (GPX) were determined. Altera tions in CuZnSOD and CAT were noted in BBL males only as compared to B BNL males and BBL and BBNL females. CuZnSOD and CAT activities were si gnificantly lower in BBL males. GPX showed a similar trend. The change s in pancreatic antioxidant enzymes precede overt hyperglycemia in mal e rats at risk for development of diabetes and may result in increased beta-cell vulnerability to oxygen-derived free radical destruction.