(R)-ACX is a novel sufonylurea compound with potent, quick and short-lasting hypoglycemic activity.
We investigated the mechanism of the hypoglycemic effect of (R)-4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzene-sulfonamide [(R)-acetoxyhexamide; (R)-ACX], a new sulfonylurea compound. (R)-ACX potently stimulated the release of insulin from cultured pancreatic beta-cells (HIT T15 cells), established from hamster islet cells SV40-transformed. When (R)-ACX was orally administered to fasted rats, it decreased the plasma glucose level in a dose-dependent manner. The hypoglycemic effect of (R)-ACX was quick and short lasting, as compared to that of acetohexamide and glibenclamide. The quick and short-lasting hypoglycemic effect of (R)-ACX was thought likely to result from rapid absorption of (R)-ACX and rapid elimination of (R)-ACX and its metabolite, (R)-hydroxyhexamide. Furthermore, (R)-ACX was found to suppress the increase of blood glucose level due to starch loading in fasted mice. (R)-ACX may be useful in the control of postprandial hyperglycemia to patients with non-insulin-dependent diabetic mellitus.
Seri
K
K
Central Research Laboratory, Godo Shusei, 250, Nakahara, Kamihongo, Matsudo, Japan.
Sanai
K
K
Kurashima
K
K
Imamura
Y
Y
Akita
H
H
D000092:Acetohexamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017208:Rats, Wistar; D013453:Sulfonylurea Compounds / Q000378:metabolism / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000092:Acetohexamide; D001786:Blood Glucose; D005905:Glyburide; D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; C406484:4-(1-acetoxyethyl)-N-(cyclohexylcarbamoyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C020362:hydroxyhexamide