Glucose tolerance and insulin resistance in the JCR : LA-corpulent rat: Effect of miglitol (Bay m1099)

A standardized meal tolerance test (MTT) using 5 g rat chow provides a sens itive index of insulin and glucose metabolism in the insulin-resistant, hyp erinsulinemic, hypertriglyceridemic, and atherosclerosis-prone JCR:LA-corpu lent (cp) strain of rats. The MTT revealed differences in insulin/glucose m etabolism that were not evident in either an intravenous (IVGTT) or intrape ritoneal (IPGTT) glucose tolerance test. The glycemic response of control r ats to a 5-g carbohydrate test meal containing miglitol (Bay m1099) was sha rply reduced, with a 50% effective dose (ED50) Of 36.4 +/- 7.5 mg/100 g foo d. At a dose of 60 mg/100 g food, the plasma glucose curve was flat and ind istinguishable from that found in the nonfed state. The plasma insulin resp onse was similarly reduced, with an ED50 Of 42.8 +/- 14.8 mg/100 g food. Ob ese male rats were treated with miglitol at 60 mg/100 g food from 6 to 12 w eeks of age. Treated rats had a significantly reduced food consumption and lower body weight at 12 weeks of age (P < .05). The treatment resulted in n o significant changes in serum lipid concentrations. When subjected to the MTT using control (non-miglitol-containing) food. treated rats demonstrated markedly improved insulin sensitivity, with a greatly reduced insulin resp onse, which may reflect an improved hepatic glucose metabolism. The results confirm that miglitol is highly effective in this obese insulin-resistant animal model. It reduced postprandial glycemic and insulin responses, and o n long-term treatment, it improved glucose and insulin metabolism. These be neficial metabolic changes suggest that miglitol may have vascular protecti ve effects in insulin-resistant states. Copyright (C) 1999 by W.B. Saunders Company.