Peroxidative stress in diabetic blood vessels. Reversal by pancreatic islet transplantation.
Diabetic complications are believed to arise, in part, through an increase in oxidative stress. We characterized antioxidant status in vascular tissue in untreated diabetic rats and in diabetic rats rendered euglycemic by pancreatic islet transplantation. Three key endogenous antioxidant enzymes (e.g., superoxide dismutase, catalase, and glutathione peroxidase) were measured. Sprague-Dawley rats with streptozotocin-induced diabetes were killed after 8 weeks of untreated hyperglycemia and compared with age-matched controls. Eight weeks of untreated diabetes resulted in a significant increase of tissue catalase in aorta, iliac artery, and femoral artery as compared with controls. No significant changes in either superoxide dismutase or glutathione peroxidase were observed in aorta, iliac artery, or femoral artery of diabetic animals. This increase in catalase in diabetic vascular tissue suggests increased oxidative stress due to chronic exposure to H2O2 in vivo. To assess the impact of islet transplantation on oxidative stress in vascular tissue, inbred Lewis strain rats were rendered diabetic with streptozotocin. After 8 weeks of untreated diabetes, rats received an intraportal islet isograft and were monitored for 4 subsequent weeks of euglycemia. Islet transplantation improved weight gain and normalized blood glucose and total glycosylated hemoglobin. While catalase was significantly increased in aorta and iliac artery at 8 and 12 weeks of diabetes, vascular catalase was restored to normal by islet transplantation. These data suggest that islet transplantation is an effective treatment strategy to minimize increased oxidative stress in diabetic vasculature.
Pieper
G M
GM
Department of Transplant Surgery, Medical College of Wisconsin, Milwaukee 53226, USA.
Jordan
M
M
Dondlinger
L A
LA
Adams
M B
MB
Roza
A M
AM
D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001158:Arteries / Q000201:enzymology / Q000503:physiopathology*; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology* / Q000601:surgery*; D005263:Femoral Artery / Q000503:physiopathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D007083:Iliac Artery / Q000503:physiopathology; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D018384:Oxidative Stress; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors; D014185:Transplantation, Isogeneic
D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase