F2-isoprostane evidence of oxidant stress in the insulin resistant, obese Zucker rat: effects of vitamin E.
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.
Laight
D W
DW
The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, UK. d.w.laight@mds.qmw.ac.uk
Desai
K M
KM
Gopaul
N K
NK
Anggård
E E
EE
Carrier
M J
MJ
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control; D006946:Hyperinsulinism / Q000097:blood / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000097:blood* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011924:Rats, Zucker; D014810:Vitamin E / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost