EFFECT OF A NEW HYPOGLYCEMIC AGENT, A-4166 4-ISOPROPYL-CYCLOHEXANECARBONYL)-D-PHENYLALANINE], ON POSTPRANDIAL BLOOD-GLUCOSE EXCURSION - COMPARISON WITH VOGLIBOSE AND GLIBENCLAMIDE

ns-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new n onsulfonylurea hypoglycemic agent that lowers blood glucose by stimula ting insulin release. In the present study, vee examined the effects o f A-4166, voglibose (an alpha-glucosidase inhibitor), and glibenclamid e (a sulfonylurea) on tile postprandial glycemic increase in rats with or without diabetes mellitus, Oral administration of A-4166 (25-100 m g/kg) dose-dependently decreased blood glucose with a rapid onset and short duration in normal rats, On the other hand, glibenclamide (1-4 m g/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect, In the case of postprandial glucose excursi on, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sust ained hypoglycemia in both normal and neonatal streptozotocin-induced diabetic rats, However, the efficacy of voglibose varied with the type of carbohydrate load. Glibenclamide produced a prolonged decrease in blood glucose without any appreciable effect on the initial glucose ex cursion, After sucrose loading, plasma insulin levels during the initi al 1 h were significantly higher in A-4166-treated rats than in contro l rats, while voglibose completely inhibited the insulin response to s ucrose, In g2iboilel amide-treated rats, an augmented insulin response was not seen, in conclusion, unlike other hypoglycemic agents, A-4166 suppresses postprandial glucose excursions by stimulating the early p hase of insulin secretion.