{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:04:24Z","timestamp":1791558264375,"version":"4.3.4"},"reference-count":0,"publisher":"American Diabetes Association","issue":"4","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.2337\/diabetes.48.4.927","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"927-932","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":395,"title":["Hyperglycemia causes oxidative stress in pancreatic beta-cells of GK rats, a model of type 2 diabetes."],"prefix":"10.2337","volume":"48","author":[{"given":"Y","family":"Ihara","sequence":"first","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Toyokuni","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Odaka","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Hiai","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Seino","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan. ihara@metab.kuhp.kyoto-u.ac.jp"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/48\/4\/927\/10585\/Hyperglycemia-causes-oxidative-stress-in","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/48\/4\/927\/10585\/Hyperglycemia-causes-oxidative-stress-in","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T06:36:42Z","timestamp":1647067002000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/48\/4\/927\/10585\/Hyperglycemia-causes-oxidative-stress-in"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4,1]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1999,4,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diabetes.48.4.927","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,4,1]]}}}