Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide.
(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166) is a new nonsulfonylurea hypoglycemic agent that lowers blood glucose by stimulating insulin release. In the present study, we examined the effects of A-4166, voglibose (an alpha-glucosidase inhibitor), and glibenclamide (a sulfonylurea) on the postprandial glycemic increase in rats with or without diabetes mellitus. Oral administration of A-4166 (25-100 mg/kg) dose-dependently decreased blood glucose with a rapid onset and short duration in normal rats. On the other hand, glibenclamide (1-4 mg/kg) showed a slower onset of its hypoglycemic action, and voglibose (0.2 mg/kg) had no effect. In the case of postprandial glucose excursion, the carbohydrate-induced increase in blood glucose was reduced by oral administration of either A-4166 or voglibose without causing sustained 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 excursion. After sucrose loading, plasma insulin levels during the initial 1 h were significantly higher in A-4166-treated rats than in control rats, while voglibose completely inhibited the insulin response to sucrose. In glibenclamide-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 phase of insulin secretion.
Ikenoue
T
T
Central Research Laboratories, Ajinomoto Co., Inc., Kanagawa, Japan.
Okazaki
K
K
Fujitani
S
S
Tsuchiya
Y
Y
Akiyoshi
M
M
Maki
T
T
Kondo
N
N
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003510:Cyclohexanes / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019518:Postprandial Period; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000008:administration & dosage
D001786:Blood Glucose; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D000077715:Nateglinide; D010649:Phenylalanine; D007294:Inositol; D013395:Sucrose; D005947:Glucose; C102817:voglibose; D005905:Glyburide