Biphasic Modulation of K+ Permeability in Pancreatic Islets During Acute Stimulation with Glucose

Abstract

The regulation of 86Rb+ efflux (marker of K+ permeability) during acute secretagogic stimulation with glucose was studied with cultured as well as freshly isolated pancreatic islets from rats and freshly isolated islets from mice. A perifusion system with minimal dead-space and "flow-through" characteristics conductive to abrupt, steep increases in ambient glucose was combined with multiple samplings of effluent to achieve high temporal resolution. Under these conditions, acute increases in perifusate glucose concentration from 4 to 16.7 mM or from 1 to 27.8 mM effected a biphasic change of the 86Rb+ fractional efflux rate. A rapid reduction of 86Rb+ efflux was interrupted by an evanescent increase in 86Rb+ outflow, which appeared to be temporally coincident with the initiation of the first phase of stimulated insulin release. It is suggested that the glucose-induced biphasic oscillations in K+ permeability may contribute to the well-known initial biphasic changes in beta-cell membrane potential and insulin release during the inception of beta-cell stimulus secretion coupling.