PIOGLITAZONE INCREASES INSULIN SENSITIVITY, REDUCES BLOOD-GLUCOSE, INSULIN, AND LIPID-LEVELS, AND LOWERS BLOOD-PRESSURE IN OBESE, INSULIN-RESISTANT RHESUS-MONKEYS

The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6 spontaneously obese, insulin-resistant rhesus monkeys. The animal s were studied during six successive 2-wk treatment phases separated b y 2-wk rest periods: two placebo phases; 0.3, 1.0, and 3.0 mg . kg(-1) day(-1) pioglitazone hydrochloride phases; and a final placebo phase. During the second week of each treatment phase, serum insulin (immuno reactive insulin [IRI]), plasma glucose, and serum triglyceride (To) l evels were measured after an overnight fast and after a standardized m eal. Blood pressure was measured and glucose tolerance tests (modified minimal model protocol) were performed a few days after the meal test s. Pioglitazone hydrochloride significantly improved fasting and postp randial levels of IRI, plasma glucose, and To in a dose-related manner (P < 0.05). Fasting values during treatment with 3.0 mg . kg(-1) day( -1) were reduced by 64% for IRI, 19% for plasma glucose, and 44% for T o compared with the placebo phase before treatment. Efficacy of piogli tazone hydrochloride was more marked for those animals with fasting hy perglycemia. Insulin sensitivity was increased by pioglitazone hydroch loride (P = 0.05), whereas glucose effectiveness and glucose disappear ance rate were not detectably affected. Systolic and mean arterial blo od pressures were significantly decreased by pioglitazone hydrochlorid e (P < 0.05). No toxic side effects of pioglitazone hydrochloride trea tment were noted.