Selective Inhibition of Glucose-Stimulated β-Cell Activity by an Anion Channel Inhibitor

Abstract.

4,4′-dithiocyanatostilbene-2,2′-disulfonic acid (DIDS), an inhibitor of the volume-sensitive anion channel, was used to investigate the role of this channel in the stimulation of rat pancreatic β-cells by glucose and by tolbutamide. Glucose-stimulated electrical activity in β-cells was markedly and reversibly inhibited by DIDS. The increase in cytosolic [Ca²⁺] and stimulated insulin release evoked by glucose were also inhibited by DIDS. In contrast to its inhibitory effect on glucose-induced β-cell activity, DIDS had no effect on electrical activity, the rise in [Ca²⁺] _i or insulin release induced by tolbutamide.

DIDS failed to increase β-cell input conductance, an index of whole-cell K _ATP channel activity, or the rate of efflux of ⁸⁶Rb⁺ from perifused islets, a measure of net K⁺ permeability. Furthermore, DIDS had no effect on intracellular pH or on regulatory volume increase following exposure of cells to hypertonic solutions, indicating that the effects of DIDS were not the result of inhibition of Cl⁻ transport systems. It is suggested that the DIDS-induced repolarization is caused by inactivation of the volume-sensitive anion channel. The stimulation of β-cell electrical and secretory activity by glucose, but not tolbutamide, may therefore involve activation of the anion channel.