F-2-isoprostane evidence of oxidant stress in the insulin resistant, obeseZucker rat: effects of vitamin E

We have concurrently investigated oxidant stress, glucose tolerance and glu cose-stimulated insulin responses in the obese Zucker rat, a widely used mo del of insulin resistance. The plasma level of the lipid peroxidation produ ct 8-epi-prostaglandin F-2 alpha, a sensitive in vivo marker of oxidant str ess, was elevated approximately 5-fold in 13-week old obese relative to age -matched, insulin-sensitive lean Zucker rats. Supplementation of the diet w ith vitamin E (as (+/-)-alpha-tocopherol acetate, 0.5% w/w) for 4 weeks, re duced plasma 8-epi-prostaglandin F-2 alpha and concomitantly reversed gluco se-stimulated hyperinsulinaemia in the obese Zucker rat without worsening g lucose tolerance. We therefore provide evidence of oxidant stress, measured as elevated plasma 8-epi-prostaglandin F-2 alpha, for the first time in th e obese Zucker rat which now provides a rationale for the beneficial effect s of antioxidants on insulin action previously reported in this model of in sulin resistance. (C) 1999 Elsevier Science B.V. All rights reserved.