AIMTo investigate the ameliorations of pioglitazone, a member of the thiazolidinedione group of antidiabetic agents, on insulin resistance in spontaneous OLETF rats with impaired glucose tolerance (IGT-OLETF).

METHODSOne group of IGT-OLETF rats was orally administered pioglitazone at the dose of 20 mg x kg(-1) (qd) for 2 weeks. Another group was given the same volume of solvent as control. Glucose tolerance and insulin tolerance were tested, and blood glucose concentrations, insulin levels and lipids in serum, liver and muscle were determined. Insulin sensitive index (ISI) was calculated by the reciprocal of fasting blood glucose times fasting insulin.

RESULTSPioglitazone was shown to markedly enhance the glycemic response to exogenous insulin (0. 4 x kg(-1), sc) in the model. The falls of blood glucose at 40 and 90 min in the insulin tolerance test were augmented by 70% and 158% in the treated group than the control. The serum insulin levels were significantly decreased and the ISI nearly normalized after treatment. Pioglitazone also lowered the serum TG and FFA levels and the lipids in liver and muscle. No effect was found on the expression of leptin in epididymal adipose tissues and on the activity of GFAT, a key enzyme in hexosamine biosynthesis pathway (data were not shown).

CONCLUSIONPioglitazone can improve the insulin resistance state in IGT-OLETF rats. Correction of lipid disorder may be associated with it.