title: The glucokinase activator GKA50 causes an increase in cell volume and activation of volume-regulated anion channels in rat pancreatic β-cells.
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.
authors.affiliation: Faculty of Life Sciences and Medicine, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Lisa
authors.initials: L
authors.lastname: McGlasson
authors.forename: Len
authors.initials: L
authors.lastname: Best
authors.forename: Peter D
authors.initials: PD
authors.lastname: Brown
mesh_terms: D000818:Animals; D001692:Biological Transport; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009579:Nitrobenzoates / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050994:Voltage-Dependent Anion Channels / Q000187:drug effects*
chemical_list: D009579:Nitrobenzoates; D011725:Pyridines; D050994:Voltage-Dependent Anion Channels; C520311:glucokinase activator compound 50; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D005941:Glucokinase; D005947:Glucose