Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies.
Repaglinide is a new carbamoylmethyl benzoic acid derivative that is structurally related to meglitinide. In common with all active oral hypoglycaemic agents, it displays a comparable U-shaped configuration. Repaglinide exerts its effects by binding to a site on the plasma membrane of beta-cells, thereby closing ATP-sensitive potassium channels. This causes depolarization of the beta-cell and the opening of voltage-sensitive calcium channels allowing the influx of extracellular calcium ions. This increase in intracellular calcium, in turn, stimulates insulin release. The insulinotropic effect of repaglinide is not related to its ionophoretic capacity. Repaglinide does not cause insulin release in the absence of exogenous glucose, nor does it inhibit the biosynthesis of proinsulin. In vivo administration of an ester of succinic acid potentiates the insulin secretory response to concomitantly administered repaglinide. Repaglinide causes a more rapid increase in plasma insulin levels in rats than either glibenclamide or glimepiride.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
D000284:Administration, Oral; D000818:Animals; D002219:Carbamates / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats
D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide