Oxidative Stress in Young Zucker Rats with Impaired Glucose Tolerance is Diminished by Acarbose

Abstract

Aims/hypothesis: There is evidence that acarbose reduces the risk for development of diabetes and cardiovascular complications. The mechanism underlying the vasculoprotective effect is however not known. We hypothesized that vasculoprotection observed by acarbose may be the consequence of a diminished generation of oxidative stress. Methods: Lean and obese Zucker rats received a diet containing 10% sucrose for 7 days. A part of the rats was treated with acarbose (15 mg/kg/day in chow). Blood glucose, plasma insulin, lipid peroxides, and as a more specific marker of oxidative stress, 8-isoprostanes, were analyzed. As cellular markers of oxidative stress we determined the activities of mitochondrial aconitase and NADPH-oxidase in aorta, heart, and kidney. In addition, poly(ADP-ribose) polymerase activity (PARP) was measured in aorta. Results: Sucrose feeding of obese Zucker rats resulted in increased blood glucose levels, plasma insulin, lipid peroxides and 8-isoprostanes. Mitochondrial aconitase was reduced; the activities of NAPDH-oxidase and PARP were enhanced. Treatment of obese Zucker rats with acarbose largely prevented these changes, whereas it had no effect in lean sucrose fed rats. Conclusion: Specifically in obese Zucker rats sucrose feeding is associated with an increased oxidative stress. The data provide in vivo evidence that mitochondria play a role in the generation of reactive oxygen species (ROS) in insulin resistant, hyperglycaemic states. Activation of PARP by ROS may be an important mediator of vascular dysfunction in insulin resistance. Treatment with acarbose is helpful to prevent the increase in oxidative stress and vascular dysfunction induced by hyperglycemia.

Key words

Zucker rats - type 2 diabetes - reactive oxygen species - aconitase - acarbose - PARP - hyperglycemia - insulin resistance

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