Because troglitazone, like leptin, lowers the triglyceride (TG) content of pancreatic islets, we searched for other leptinomimetic actions, Leptin upregulates the expression of uncoupling protein-2 (UCP-2) mRNA in islets of normal rats, but has no effect in islets of obese Zucker Diabetic Fatty (ZDF) rats with mutated leptin receptors. We report here that troglitazone also increases the UCP-2/beta-actin mRNA ratio by 115% in wild type ZDF rats and by 400% in obese ZDF rats. (C) 1997 Academic Press.