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Calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate dihydrate (KAD-1229) was found to have potent hypoglycemic effects. This study was designed to elucidate its mechanisms by comparing its action with those of the antidiabetic hypoglycemic agents known as sulfonylureas in vivo and in vitro. In fasted beagles, oral administration of 0.1(More)
This is the first systematic study on the pancreatic beta cell function in the heterozygous mouse with targeted disruption of the beta cell glucokinase gene. The heterozygotes' beta cell displayed the following characteristics: (1) impaired glucose sensitivity with normal glucose responsiveness, (2) poor discrimination of alpha and beta glucose anomers, and(More)
Adult C57BL/10 mice (H-2b Fv-1b) inoculated with LP-BM5 murine leukemia virus develop a disease which has many features in common with human acquired immunodeficiency syndrome (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency. In the present study, we examined the possibility that this murine AIDS (MAIDS) model would be useful(More)
We studied the mechanism of action of KAD-1229, a non-sulfonylurea compound shown to stimulate insulin secretion, in a glucose responsive insulinoma cell line, MIN 6 cells. In microsomal fraction of MIN 6 cells, KAD-1229 displaced binding of [3H]glibenclamide in a concentration-dependent manner. The dissociation constant and the maximum binding capacity(More)
We investigated therapeutic effects of a rapid- and short-acting non-sulfonylurea hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate (KAD-1229), on streptozotocin (STZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. The effects exerted by KAD-1229 on the post-prandial plasma glucose rise in(More)
Erythropoietin (EPO), a glycoprotein produced mainly by the kidney, is the major physiological regulator of erythropoiesis. We developed a sensitive and rapid ELISA for measurement of rat serum EPO with two monoclonal antibodies that recognize different epitopes. To understand the mechanism by which erythropoiesis is impaired in rats deficient in dietary(More)
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(More)
1. We examined the cooperative effect of a newly synthesized oral hypoglycaemic agent, KAD-1229 with glucose on insulin, glucagon and somatostatin secretion in the isolated perfused pancreas of the rat. 2. KAD-1229 stimulated concentration-dependently the first phase of insulin secretion without the second phase in the presence of 2.8 mM glucose, while it(More)
We have investigated the hypoglycemic effects of the newly synthesized short-acting nonsulphonylurea hypoglycemic agent calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)-propionate dihydrate (KAD-1229) in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM rats that were given a neonatal injection of 60 mg/kg streptozotocin showed a(More)
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