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 re gulating glucose and lipid metabolism in insulin-resistant obese Zucke r rats and to compare obese rats with lean controls with respect to ch anges in insulin sensitivity. DESIGN: Animal study of lean and obese r ats with or without insulin sensitizer, YM268. ANIMALS: Nine week old male lean (Fa/-) and obese (fa/fa) Zucker rats. MEASUREMENTS: Plasma g lucose, insulin, triglyceride (TG), non-esterified fatty acid (NEFA), cholesterol at baseline and after 14 d, the dose of YM268 for exhibiti ng a 30% decrease in each parameter (ED(30)). RESULTS: Insulin, TG, an d NEFA concentrations were approximately 2-6 times higher in obese rat s. YM268 had no effect on glucose but decreased insulin in lean and ob ese rats with ED(30) of 3.0 and 2.9 mg/kg. YM268 also reduced TG and N EFA in lean and obese rats [ED(30) (mg/kg): lean; 4.1 (TG), 5.0 (NEFA) , obese; 2.1, 3.0]. A significant correlation of either TG or NEFA lev el to insulin was established in lean and obese rats. CONCLUSION: Plas ma TG and NEFA, but not cholesterol concentration, are dependent on pl asma insulin in lean and obese Zucker rats, and insulin sensitivity wi th respect to TG and NEFA metabolism in obese rats may not be differen t from that in lean rats.