TREATMENT WITH THE THIAZOLIDINEDIONE (BRL-49653) DECREASES INSULIN-RESISTANCE IN OBESE ZUCKER HINDLIMB

Hindlimbs of mature age obese fa/fa Zucker rats were perfused and foun d to be markedly insulin-resistant when com pa red to the hindlimbs of age-matched lean Fa/? animals. Hindlimb analysis also showed a greate r content of fat and a lower content of muscle in the obese. Treatment of the obese animals for 7 days with the thiazolidinedione, BRL 49653 (3 mu mol/kg/day) significantly decreased the insulin resistance of t he hindlimb and significantly increased the rate of weight gain in the whole rat. However, the decreased insulin resistance due to BRL 49653 could not be accounted for by an increase in the proportion of hindli mb muscle to fat or by an increase in the hindlimb muscle mass perfuse d.