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

Abstract

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.

Involvement of Protein Kinase C β2 in c-mycInduction by High Glucose in Pancreatic β-Cells

“…These results are consistent with previous results showing that c-myc expression is induced after partial pancreatectomy model of diabetes and in rats maintained with a hyperglycemic clamp (9,10). Since the diabetic state is associated with PKC activation (13)(14)(15)(16)(17)(18)(19)(20) and the production of reactive oxygen species in several cell types (27)(28)(29)(30)(31), the involvement of PKC and oxidative stress in c-myc induction was studied. As shown in Fig.…”

Study of urinary 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage in diabetic nephropathy patients

“…The high urinary 8-OHdG levels in the patients with high albuminuria investigated in this study suggested that the increased oxidative stress has a primary role in the pathogenesis of diabetic nephropathy. Recent reports found an increased systemic oxidative stress in diabetic patients and in diabetic animal models [13,[21][22][23]. Our study showed that the patients with normoalbuminuria had a lower urinary 8-OHdG level than the patients with high albuminuria.…”

Soybean oil treatment impairs glucose-stimulated insulin secretion and changes fatty acid composition of normal and diabetic islets

“…3a) when compared with untreated normal animals. It has been reported that impaired GSIS observed in GK rats is associated with alterations in β-cell glucose metabolism, protein kinase C pathway, modulation of UCP-2 expression, acetylcholine and oxidative stress [11,26,[47][48][49]. However, it can also be associated with fatty acid content alterations.…”