Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats,a model of type 2 diabetes

Reactive oxygen species are involved in a diversity of biological phenomena such as inflammation, carcino-genesis, aging, and atherosclerosis. We and other investigators have shown that the level of 8-hydroxy-2'-deoxyguanosin e (8-OHdG), a marker for oxidative stress, is increased in either the urine or the mononuclear cells of the blood of type 2 diabetic patients. However , the association between type 2 diabetes and oxidative stress in the pancr eatic beta-cells has not been previously described. We measured the levels of 8-OHdG and 4-hydroxy-2-nonenal (HNE)-modified proteins in the pancreatic beta-cells of GK rats, a model of nonobese type 2 diabetes. Quantitative i mmunohistochemical analyses with specific antibodies revealed higher levels of 8-OHdG and HNE-modified proteins in the pancreatic beta-cells of GK rat s than in the control Wistar rats, with the levels increasing proportionall y with age and fibrosis of the pancreatic islets. We further investigated w hether the levels of 8-OHdG and HNE-modified proteins would be modified in the pancreatic beta-cells of GK rats fed with 30% sucrose solution or 50 pp m of voglibose (alpha-glucosidase inhibitor). In the GK rats, the levels of 8-OHdG and HNE-modified proteins, as well as islet fibrosis, were increase d by sucrose treatment but reduced by voglibose treatment. These results in dicate that the pancreatic beta-cells of GK rats are oxidatively stressed, and that chronic hyperglycemia might be responsible for the oxidative stres s observed in the pancreatic beta-cells.