Metabolic effects of troglitazone on fat-induced insulin resistance in the rat

• Published in: Metabolism, clinical and experimental Vol. 44; no. 11; pp. 1489 - 1494
• Main Authors: Khoursheed, Mousa, Miles, Philip D.G., Gao, Ke-Ming, Lee, Moon-Kyu, Moossa, A.R., Olefsky, Jerrold M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-11-1995; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Pressure - physiology; Body Weight - physiology; Chromans - blood; Chromans - metabolism; Chromans - pharmacology; Dietary Fats - toxicity; Eating - physiology; General and cellular metabolism. Vitamins; Glucose - metabolism; Glucose Clamp Technique; Hyperinsulinism - blood; Hyperinsulinism - metabolism; Hypoglycemic Agents - blood; Hypoglycemic Agents - metabolism; Hypoglycemic Agents - pharmacology; Insulin - metabolism; Insulin Resistance - physiology; Lipids - blood; Liver - metabolism; Male; Medical sciences; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Thiazoles - blood; Thiazoles - metabolism; Thiazoles - pharmacology; Thiazolidinediones; Troglitazone; Endocrinopathy; Hyperinsulinemia; Pancreatic hormone; Pharmacological activity; Rat; Rodentia; Non insulin dependent diabetes; Insulin; Biological activity; Protein hormone; Target tissue resistance; Hypoglycemic agent; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/0026-0495(95)90151-5

Troglitazone is a new orally active hypoglycemic agent that has been shown to ameliorate insulin resistance and hyperinsulinemia in both diabetic animal models and non—insulin-dependent diabetes mellitus (NIDDM) subjects. To determine whether this drug could prevent the development of diet-induced insulin resistance and related abnormalities, we studied its effect on insulin resistance induced by high-fat feeding in rats. Normal male Sprague-Dawley rats were fed a high-fat diet for 3 weeks with and without troglitazone as a food mixture (0.2%) or were fed normal chow. In vivo insulin action was measured using a euglycemic-hyperinsulinemic clamp at two different insulin infusion rates, 4 (submaximal stimulation) and 40 (maximal stimulation) mU/kg/min. Fat feeding markedly reduced the submaximal glucose disposal rate ([GDR], 26.4 ± 1.3
v 37.5 ± 1.4 mg/kg/min,
P < .01) and maximal GDR (55.9 ± 1.3
v 64.5 ± 1.3 mg/kg/min,
P < .05), reduced the suppressibility of submaximal hepatic glucose production ([HGP], 3.2 ± 0.9
v 1.5 ± 0.5 mg/kg/min,
P < .05), and resulted in hyperlipidemia. Troglitazone treatment did not affect any of these parameters. Insulin resistance induced by fat feeding is the first experimental model in which troglitazone failed to correct or partially correct the insulin resistance.