Troglitazone Improves Insulin-Stimulated Glucose Utilization Associated with an Increased Muscle Glycogen Content in Obese Zucker Rats.

Abstract

Recent studies have demonstrated that troglitazone has the capacity to improve insulin resistance. The present study was undertaken to determine the effect of troglitazone on in vivo insulin action, the activities of the pyruvate dehydrogenase (PDH) complex and 3-hydroxyacyl-CoA dehydrogenase (3-HADH) in muscle, and muscle GLUT-4 and glycogen content in obese and lean Zucker rats. Rats were fed a normal chow diet with and without troglitazone as a food admixture (0.2%) for 3 weeks. In vivo insulin action was measured by the sequential euglycemic clamp technique at two different insulin infusion rates (6 and 30mU/kg BW/min). At the basal (fasting) state and after the clamp studies, the activities of PDH complex and 3-HADH, and the amounts of GLUT-4 and glycogen contained in the red gastrocnemius muscles were determined. Troglitazone treatment produced a significant rise in the metabolic clearance rate of glucose (MCR) during the 6-mU/kg BW/min insulin clamp study (19.5±3.9 vs 9.9±1.5ml/kg BW/min, mean±SE, P<0.05) in obese rats, but not in lean rats. Troglitazone significantly increased the muscle glycogen content after the clamp study, compared to non-treated rats, in obese rats (9.9±0.5vs 6.5±0.4mg/g tissue, P<0.05) and has the tendency to increase the activity state of PDH complex in obese and lean rats at the fasting state. However, no effect of the drug on muscle GLUT-4 content was found. These results indicate that troglitazone may improve insulin sensitivity associated with increased muscle glycogen content.