IN-VITRO INSULINOTROPIC ACTION OF A NEW NON-SULFONYLUREA HYPOGLYCEMIC AGENT, CALCIUM (2S)-2-BENZYL-3-(CIS-HEXAHYDRO-2-ISOINDOLINYL-CARBONYL) PROPIONATE DIHYDRATE (KAD-1229), IN RAT PANCREATIC B-CELLS

被引：21

作者：

OHNOTA, H ^{[1
]}

KOBAYASHI, M ^{[1
]}

KOIZUMI, T ^{[1
]}

KATSUNO, K ^{[1
]}

SATO, F ^{[1
]}

AIZAWA, T ^{[1
]}

机构：

[1] SHINSHU UNIV,SCH MED,DEPT GERIATR ENDOCRINOL & METAB,MATSUMOTO,NAGANO 390,JAPAN

来源：

BIOCHEMICAL PHARMACOLOGY | 1995年 / 49卷 / 02期

关键词：

KAD-1229; SULFONYLUREA; INSULIN SECRETION; PERFUSION OF PANCREAS;

D O I：

10.1016/S0006-2952(94)00484-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We examined the in vitro insulinotropic action of a novel non-sulfonylurea compound, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), which is a succinate derivative, using rat pancreatic islets and perfused pancreas. The sodium salt of KAD-1229 free acid (KAD-1229-Na) stimulated insulin secretion from isolated rat islets and perfused rat pancreas in a concentration-dependent manner at 0.1 to 10 mu M. It produced a predominant first phase and a less prominent second phase response in the presence of 5.55 mM glucose. An ATP-sensitive K+ (K-ATP(+)) channel activator, diazoxide, eliminated the insulinotropic effect of KAD-1229-Na. Glucose primed the B-cell in the perfused pancreas, but KAD-1229-Na did not. When the insulinotropic effects of 16.7 mM glucose on isolated rat islets were inhibited submaximally by 1 mu M norepinephrine, the addition of 1 mu M KAD-1229-Na reversed this inhibition. All of these insulinotropic effects of KAD-1229-Na were qualitatively indistinguishable from those of sulfonylurea compounds. We conclude that KAD-1229-Na acts on K-ATP(+) channels of pancreatic B-cells despite its non-sulfonylurea structure.

引用

页码：165 / 171

页数：7

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