The glucokinase activator GKA50 causes an increase in cell volume and activation of volume-regulated anion channels in rat pancreatic β-cells

Glucokinase plays a key role in the metabolism of glucose by pancreatic β-cells. In this study the effects of the glucokinase activator GKA50 on cell volume and electrical activity in rat β-cells were examined. One micro molar GKA50 caused an increase in β-cell volume in the presence of 4 mM glucose. GKA50 also caused a depolarisation of β-cell membrane potential and increased electrical activity. These changes were associated with the activation of inward whole-cell currents, and were attenuated by the anion channel inhibitor 5-nitro-2-(3-phenylpropylamino) benzoic acid. In single channel experiments, the open probability of volume-regulated anion channels (VRAC) was increased from 0.03 ± 0.01 to 0.19 ± 0.04 (n = 3) by the GKA50. The data suggest that a GKA50-evoked increase in glucose metabolism causes an increase in β-cell volume. This in turn activates VRAC leading to a depolarisation of the cell membrane potential.

► The effects of GKA50 on pancreatic β-cells were examined. ► GKA50 caused a metabolism-dependent increase in β-cell volume. ► GKA50-induced swelling activates volume-regulated anion channels. ► GKA50 evoked a sustained depolarisation of β-cell membrane potential.