Changes in Pancreatic Glutathione Peroxidase and Superoxide Dismutase Activities in the Prediabetic Diabetes-Prone BB Rat

Abstract

Pancreatic superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities were measured during the development of diabetes in diabetesprone BB rats (BBdp) prior to insulin dependence. The pancreata from seven to eight BBdp rats of each sex were examined at ages 5, 7, 10, and 18 weeks and compared with age-matched control BB rats (BBc). At Week 18, BBdp rats had moderate to high Insulitis but normal levels of blood glucose and insulin. Pancreatic CuZnSOD activity in BBdp rats was two times higher than the activity seen in BBc rats at age 5–10 weeks but then declined to the same level as seen in BBc rats at 18 weeks of age. MnSOD activity Increased over time in the BBdp rats but remained very low in BBc rats. These changes in CuZnSOD and MnSOD activity resulted in BBdp rats having twice the pancreatic total SOD activity compared with BBc rats (P < 0.0001). Total GSHPx activity was significantly reduced in the pancreata from both male and female BBdp rats compared with their respective controls (P < 0.01 and P < 0.0001, respectively). The lower total GSHPx activity was due to reduced selenium-dependent GSHPx (SeGSHPx) activity. Erythrocyte and plasma activity of these enzymes was not different between rats with or without insulitis, indicating that differences in enzyme activities were confined to the pancreas. Thus, changes in pancreatic antioxidant enzyme activities occur prior to the development of diabetes symptoms in BBdp rats and may be related to the destruction of the pancreatic B cells and ultimate development of diabetes.