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F2-isoprostane evidence of oxidant stress in the insulin resistant, obese Zucker rat: effects of vitamin E

Authors
Journal
European Journal of Pharmacology
0014-2999
Publisher
Elsevier
Publication Date
Volume
377
Issue
1
Identifiers
DOI: 10.1016/s0014-2999(99)00407-0
Keywords
  • Oxidant Stress
  • Insulin Resistance
  • Obese
  • Zucker Rat
  • Diabetes Mellitus

Abstract

Abstract We have concurrently investigated oxidant stress, glucose tolerance and glucose-stimulated insulin responses in the obese Zucker rat, a widely used model of insulin resistance. The plasma level of the lipid peroxidation product 8-epi-prostaglandin F 2α, a sensitive in vivo marker of oxidant stress, was elevated approximately 5-fold in 13-week old obese relative to age-matched, insulin-sensitive lean Zucker rats. Supplementation of the diet with vitamin E (as (±)-α-tocopherol acetate, 0.5% w/w) for 4 weeks, reduced plasma 8-epi-prostaglandin F 2α and concomitantly reversed glucose-stimulated hyperinsulinaemia in the obese Zucker rat without worsening glucose tolerance. We therefore provide evidence of oxidant stress, measured as elevated plasma 8-epi-prostaglandin F 2α, for the first time in the obese Zucker rat which now provides a rationale for the beneficial effects of antioxidants on insulin action previously reported in this model of insulin resistance.

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