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.