EFFECT OF THE NEW ORAL ANTIDIABETIC AGENT (-)-BM-13.0913.NA ON INSULIN-RESISTANCE IN LEAN AND OBESE ZUCKER RATS

The new antidiabetic agent (-)-BM 13.0913,Na (BM) was administered to 12-week-old lean and obese Zucker rats, an animal model of insulin res istance, at a daily dose of 50 mg/kg for 14 days. Hyperinsulinemic-eug lycemic clamps were performed on treated and untreated lean and obese Zucker rats. Basal hepatic glucose production (HGP) rates were similar in lean and obese untreated animals, insulin-induced suppression of H GP was significantly less effective in obese animals. In addition, the se animals exhibited the characteristic impaired glucose utilization. In obese animals, drug treatment improved insulin suppression of HGP a nd total glucose utilization (GU) during clamp studies. Furthermore, d rug treatment decreased insulin levels during clamp studies, suggestin g an acceleration of insulin clearance, Drug treatment also decreased basal plasma insulin levels and serum and liver concentrations of chol esterol in both fasted lean and obese rats, Additionally, blood glucos e, plasma nonesterified fatty acids (NEFA), and serum triglyceride lev els were reduced in fasted obese rats, but only minor changes in liver triglycerides were observed in lean and obese rats. On the basis of t hese results, we suggest that BM is an effective antidiabetic agent th at may reduce abnormalities of glucose and lipid metabolism. Copyright (C) 1995 by W.B. Saunders Company