The non-sulfonylurea moiety of gliquidone mimics the effects of the parent molecule on pancreatic B-cells.

Abstract

Compound UL-DF 9 corresponds to the non-sulfonylurea moiety of gliquidone, a hypoglycaemic sulfonylurea of the second generation. Its effects on the B-cell function were studied in vitro with mouse islets. In the presence of a non-stimulatory concentration of glucose (3 mM), UL-DF 9 decreased 86Rb+ efflux and accelerated 45Ca2+ efflux from islet cells, depolarized the B-cell membrane and induced an electrical activity similar to that triggered by stimulatory concentrations of glucose, and increased insulin release. The changes in 45Ca2+ efflux and insulin release, but not the inhibition of 86Rb+ efflux, were abolished in the absence of Ca2+. In the presence of 10 mM glucose, UL-DF 9 increased 86Rb+ and 45Ca2+ efflux from the islets, augmented the electrical activity in B-cells, and potentiated insulin release. These changes were suppressed by omission of extracellular Ca2+. Qualitatively similar effects were produced by lower concentrations of gliquidone itself. The data suggest that UL-DF 9 and gliquidone decrease the K+ permeability of the B-cell membrane, thereby causing a depolarization which leads to activation of voltage-dependent Ca channels and Ca2+ influx, and thus eventually increase insulin release. Hypoglycaemic sulfonylureas of the second generation therefore seem to contain a second chemical group that interacts with K channels of B-cells as does the sulfonylurea group itself.