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

Eur J Pharmacol. 1999 Jul 14;377(1):89-92. doi: 10.1016/s0014-2999(99)00407-0.


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 F2alpha, 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 (+)-alpha-tocopherol acetate, 0.5% w/w) for 4 weeks, reduced plasma 8-epi-prostaglandin F2alpha 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 F2alpha, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Dietary Supplements
  • Dinoprost / analogs & derivatives*
  • Dinoprost / blood
  • Hyperglycemia / blood
  • Hyperglycemia / prevention & control
  • Hyperinsulinism / blood
  • Hyperinsulinism / prevention & control
  • Insulin / blood
  • Insulin Resistance*
  • Male
  • Obesity / blood*
  • Obesity / physiopathology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Rats
  • Rats, Zucker
  • Vitamin E / pharmacology


  • Blood Glucose
  • Insulin
  • Vitamin E
  • 8-epi-prostaglandin F2alpha
  • Dinoprost