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, carcinogenesis, aging, and atherosclerosis. We and other investigators have shown that the level of 8-hydroxy-2'-deoxyguanosine (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 pancreatic 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 immunohistochemical analyses with specific antibodies revealed higher levels of 8-OHdG and HNE-modified proteins in the pancreatic beta-cells of GK rats than in the control Wistar rats, with the levels increasing proportionally with age and fibrosis of the pancreatic islets. We further investigated whether 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 ppm of voglibose (alpha-glucosidase inhibitor). In the GK rats, the levels of 8-OHdG and HNE-modified proteins, as well as islet fibrosis, were increased by sucrose treatment but reduced by voglibose treatment. These results indicate that the pancreatic beta-cells of GK rats are oxidatively stressed, and that chronic hyperglycemia might be responsible for the oxidative stress observed in the pancreatic beta-cells.
Ihara
Y
Y
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp
Toyokuni
S
S
Uchida
K
K
Odaka
H
H
Tanaka
T
T
Ikeda
H
H
Hiai
H
H
Seino
Y
Y
Yamada
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D007150:Immunohistochemistry; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D012996:Solutions; D013395:Sucrose / Q000494:pharmacology
D000447:Aldehydes; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007328:Insulin; D011506:Proteins; D012996:Solutions; D007294:Inositol; D013395:Sucrose; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; C102817:voglibose