EFFECTS OF GLIMEPIRIDE ON IN-VIVO INSULIN ACTION IN NORMAL AND DIABETIC RATS

To evaluate the effects of glimepiride on insulin action in peripheral tissues, we investigated insulin-induced glucose uptake in normal and diabetic rats using the euglycemic clamp procedure (insulin infusion rates: 6 and 30 mU/kg/min). Normal rats: After oral administration of glimepiride (0.1 mg/kg/day; NG) or saline (NC) for 2 weeks, euglycemic clamp procedures were performed. During submaximal hyperinsulinemia ( 620 +/- 35 pmol/l, mean +/- S.E.M.), metabolic clearance rates of gluc ose (MCR) in NG were significantly higher than in NC (25.1 +/- 2.1 vs. 18.3 +/- 1.2 ml/kg/min, P < 0.05). During maximal hyperinsulinemia (5 235 +/- 270 pmol/1), MCRs in NG were higher than in NC, but there was no statistical significance (43.3 +/- 2.8 and 38.9 +/- 2.8). Diabetic rats: streptozotocin-induced diabetic rats were divided into four grou ps, GI (glimepiride treatment, 0.1 mg/kg/day p.o., with insulin, 5 U/d ay s.c.), SI (insulin alone), SG (glimepiride alone), and SC (saline). MCRs in the four groups were similar during 6 mU/kg/min clamps. Durin g 30 mU/kg/min clamps, MCRs in GI were significantly higher than those in SC, SG or SI (23.4 +/- 2.8 vs. 12.2 +/- 1.9 and 8.9 +/- 0.8, P < 0 .01, and vs. 17.4 +/- 1.5, P < 0.05). Although MCRs in SI tended to be higher than in SC, there was no significant statistical difference be tween these two groups. These results suggest that glimepiride enhance s insulin action in peripheral tissues, and that glimepiride treatment with insulin improves the insulin resistance observed in streptozotoc in-induced diabetic rats.