TROGLITAZONE REDUCES FREE FATTY ACID-INDUCED INSULIN-RESISTANCE IN PERFUSED RAT HINDQUARTER

In order to study the effects of troglitazone on insulin resistance as sociated with elevated plasma free fatty acid (FFA), the hindquarters of rats treated with troglitazone for 14 days were perfused with a med ium containing 15 mmol/l glucose, 0-1,000 mu U/ml insulin, and 0 or 1. 0 mmol/l palmitate. In the absence of palmitate, net glucose uptake wa s similar between control and troglitazone-treated rat hindquarters at each insulin concentration: 47 +/- 10 and 45 +/- 9 mu mol for 30 min at 0 mu U/ml insulin; and 94 +/- 14 and 99 +/- 13 mu mol for 30 min at 1,000 mu U/ml insulin respectively. Addition of palmitate abolished i nsulin stimulation of net glucose uptake in control rat hindquarter bu t did not decrease it in troglitazone-treated rat hindquarter (60 +/- 11 vs 99 +/- 12 mu mol for 30 min at 1,000 mu U/ml insulin, p < 0.01). It is suggested that the ''FFA-tolerant effect'' is one mechanism by which troglitazone reduces insulin resistance.