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

• Published in: European journal of pharmacology 1999-07, Vol.377 (1), p.89-92
• Main Authors: LAIGHT, D. W, DESAI, K. M, GOPAUL, N. K, ÄNGGARD, E. E, CARRIER, M. J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Body Weight - drug effects; Dietary Supplements; Dinoprost - analogs & derivatives; Dinoprost - blood; General and cellular metabolism. Vitamins; Hyperglycemia - blood; Hyperglycemia - prevention & control; Hyperinsulinism - blood; Hyperinsulinism - prevention & control; Insulin - blood; Insulin Resistance; Male; Medical sciences; Obesity - blood; Obesity - physiopathology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; Rats; Rats, Zucker; Vitamin E - pharmacology
• ISSN: 0014-2999; 1879-0712
• 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.