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 sensitive index of insulin and glucose metabolism in the insulin-resistant, hyperinsulinemic, hypertriglyceridemic, and atherosclerosis-prone JCR:LA- corpulent (cp) strain of rats. The MTT revealed differences in insulin/glucose metabolism that were not evident in either an intravenous (IVGTT) or intraperitoneal (IPGTT) glucose tolerance test. The glycemic response of control rats to a 5-g carbohydrate test meal containing miglitol (Bay m1099) was sharply reduced, with a 50% effective dose (ED₅₀) of 36.4 ± 7.5 mg/100 g food. At a dose of 60 mg/100 g food, the plasma glucose curve was flat and indistinguishable from that found in the nonfed state. The plasma insulin response was similarly reduced, with an ED₅₀ of 42.8 ± 14.8 mg/100 g food. Obese male rats were treated with miglitol at 60 mg/100 g food from 6 to 12 weeks 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 no 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 response, 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 on long-term treatment, it improved glucose and insulin metabolism. These beneficial metabolic changes suggest that miglitol may have vascular protective effects in insulin-resistant states.