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.
Russell
J C
JC
Department of Surgery, University of Alberta, Edmonton, Canada.
Graham
S E
SE
Dolphin
P J
PJ
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D004195:Disease Models, Animal; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005951:Glucose Tolerance Test; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050112:Imino Pyranoses; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood* / Q000201:enzymology; D019518:Postprandial Period; D051381:Rats
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D050112:Imino Pyranoses; D007328:Insulin; D008055:Lipids; C045621:miglitol; D017485:1-Deoxynojirimycin; D005944:Glucosamine