Troglitazone reduces free fatty acid-induced insulin resistance in perfused rat hindquarter

In order to study the effects of troglitazone on insulin resistance associated with elevated plasma free fatty acid (FFA), the hindquarters of rats treated with troglitazone for 14 days were perfused with a medium containing 15 mmol/l glucose, 0-1,000 microU/ml insulin, and 0 or 1.0 mmol/l palmitate. In the absence of palmitate, net glucose uptake was similar between control and troglitazone-treated rat hindquarters at each insulin concentration: 47 +/- 10 and 45 +/- 9 mumol for 30 min at 0 microU/ml insulin; and 94 +/- 14 and 99 +/- 13 mumol for 30 min at 1,000 microU/ml insulin respectively. Addition of palmitate abolished insulin stimulation of net glucose uptake in control rat hindquarter but did not decrease it in troglitazone-treated rat hindquarter (60 +/- 11 vs 99 +/- 12 mumol for 30 min at 1,000 microU/ml insulin, p < 0.01). It is suggested that the "FFA-tolerant effect" is one mechanism by which troglitazone reduces insulin resistance.