Role of plasma insulin concentration in regulating glucose and lipid metabolism in lean and obese Zucker rats

OBJECTIVE: To determine the role of plasma insulin concentration in regulating glucose and lipid metabolism in insulin-resistant obese Zucker rats and to compare obese rats with lean controls with respect to changes in insulin sensitivity. DESIGN: Animal study of lean and obese rats with or without insulin sensitizer, YM268. ANIMALS: Nine week old male lean (Fa/–) and obese (fa/fa) Zucker rats. MEASUREMENTS: Plasma glucose, insulin, triglyceride (TG), non-esterified fatty acid (NEFA), cholesterol at baseline and after 14 d, the dose of YM268 for exhibiting a 30% decrease in each parameter (ED30). RESULTS: Insulin, TG, and NEFA concentrations were approximately 2–6 times higher in obese rats. YM268 had no effect on glucose but decreased insulin in lean and obese rats with ED30 of 3.0 and 2.9 mg/kg. YM268 also reduced TG and NEFA in lean and obese rats [ED30 (mg/kg): lean; 4.1 (TG), 5.0 (NEFA), obese; 2.1, 3.0]. A significant correlation of either TG or NEFA level to insulin was established in lean and obese rats. CONCLUSION: Plasma TG and NEFA, but not cholesterol concentration, are dependent on plasma insulin in lean and obese Zucker rats, and insulin sensitivity with respect to TG and NEFA metabolism in obese rats may not be different from that in lean rats.