Clinical Pharmacology of Sulfonylureas

Abstract

In vitro studies using the perfused rat pancreas and in vivo studies using the hyperglycemic clamp have demonstrated that sulfonylureas stimulate insulin secretion in a biphasic fashion (Loubatieres 1957; Malaisse et al. 1972; Grodsky et al. 1977; Groop et al. 1987b). The insulinotropic effect of sulfonylureas is augmented by glucose, and sulfonylureas have therefore been proposed to increase B-cell sensitivity to glucose and non-glucose stimuli rather than to increase the synthesis of insulin by the pancreatic B cell (Basabe et al. 1976; Pfeifer et al. 1980; Dunbar and Foá 1974; Grodsky et al. 1977). Sulfonylureas close ATP-dependent potassium channels, which, in turn, results in depolarization of the B cell and influx of calcium (Sturgess et al. 1985; Boyd AE III 1988). The final result is stimulation of insulin secretion. Sulfonylureas bind to receptor-like structures on the B cell, which may be closely linked to or be part of the potassium channels (Schmid-Antomarchi et al. 1987; Gaines et al. 1988; Siconolfi-Baez et al. 1990). The binding capacity of different sulfonylureas reflects their ability to stimulate insulin secretion.