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The Glucokinase Activator GKA50 Causes an Increase in Cell Volume and Activation of Volume-Regulated Anion Channels in Rat Pancreatic β-cells

The Glucokinase Activator GKA50 Causes an Increase in Cell Volume and Activation of Volume-Regulated Anion Channels in Rat Pancreatic β-cells

Lisa McGlasson, Len Best, Peter D Brown

Mol Cell Endocrinol. 2011 Aug 6;342(1-2):48-53.

PMID: 21664426

Abstract:

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 4mM 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP851884872	GKA50		851884-87-2	Price

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