Pioglitazone Increases Insulin Sensitivity, Reduces Blood Glucose, Insulin, and Lipid Levels, and Lowers Blood Pressure, in Obese, Insulin-Resistant Rhesus Monkeys

Joseph W Kemnitz; Diane F Elson; Ellen B Roecker; Scott T Baum; Richard N Bergman; Martin D Meglasson

doi:10.2337/diab.43.2.204

Original Articles

Pioglitazone Increases Insulin Sensitivity, Reduces Blood Glucose, Insulin, and Lipid Levels, and Lowers Blood Pressure, in Obese, Insulin-Resistant Rhesus Monkeys

Joseph W Kemnitz ,
Diane F Elson ,
Ellen B Roecker,
Scott T Baum,
Richard N Bergman and
Martin D Meglasson

Wisconsin Regional Primate Research Center, University of Wisconsin-Madison Madison, Wisconsin
Departments of Medicine, University of Wisconsin-Madison Madison, Wisconsin
Biostatistics, University of Wisconsin-Madison Madison, Wisconsin
Department of Physiology and Biophysics, University of Southern California Los Angeles, California
The Upjohn Company Kalamazoo, Michigan

Address correspondence and reprint requests to Dr. Joseph W. Kemnitz, Wisconsin Regional Primate Research Center, 1223 Capitol Court, Madison, Wl 53715-1299.

Diabetes 1994 Feb; 43(2): 204-211. https://doi.org/10.2337/diab.43.2.204

Abstract

The antidiabetic effects of pioglitazone hydrochloride were evaluated in 6 spontaneously obese, insulin-resistant rhesus monkeys. The animals were studied during six successive 2-wk treatment phases separated by 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 (immunoreactive insulin [IRI]), plasma glucose, and serum triglyceride (TG) levels were measured after an overnight fast and after a standardized meal. Blood pressure was measured and glucose tolerance tests (modified minimal model protocol) were performed a few days after the meal tests. Pioglitazone hydrochloride significantly improved fasting and postprandial levels of IRI, plasma glucose, and TG 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 TG compared with the placebo phase before treatment. Efficacy of pioglitazone hydrochloride was more marked for those animals with fasting hyperglycemia. Insulin sensitivity was increased by pioglitazone hydrochloride (P = 0.05), whereas glucose effectiveness and glucose disappearance rate were not detectably affected. Systolic and mean arterial blood pressures were significantly decreased by pioglitazone hydrochloride (P < 0.05). No toxic side effects of pioglitazone hydrochloride treatment were noted.