PEROXIDATIVE STRESS IN DIABETIC BLOOD-VESSELS - REVERSAL BY PANCREATIC-ISLET TRANSPLANTATION

Diabetic complications are believed to arise, in part, through an incr ease in oxidative stress. We characterized antioxidant status in vascu lar tissue in untreated diabetic rats and in diabetic rats rendered eu glycemic by pancreatic islet transplantation. Three key endogenous ant ioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathion e peroxidase) were measured. Sprague-Damley rats with streptozotocin-i nduced diabetes were killed after 8 weeks of untreated hyperglycemia a nd compared with age-matched controls. Eight weeks of untreated diabet es resulted in a significant increase of tissue catalase in aorta, ili ac artery, and femoral artery as compared with controls. No significan t changes in either superoxide dismutase or glutathione peroxidase wer e observed in aorta, iliac artery, or femoral artery of diabetic anima ls. This increase in catalase in diabetic vascular tissue suggests inc reased oxidative stress due to chronic exposure to H2O2 in vivo. To as sess the impact of islet transplantation on oxidative stress in vascul ar tissue, inbred Lewis strain rats were rendered diabetic with strept ozotocin. After 8 weeks of untreated diabetes, rats received an intrap ortal islet isograft and were monitored for 4 subsequent weeks of eugl ycemia. Islet transplantation improved weight gain and normalized bloo d glucose and total glycosylated hemoglobin. While catalase was signif icantly increased in aorta and iliac artery at 8 and 12 weeks of diabe tes, vascular catalase was restored to normal by islet transplantation . These data suggest that islet transplantation is an effective treatm ent strategy to minimize increased oxidative stress in diabetic vascul ature.