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

Lisa Mcglasson (1) , Len Best (2) , Peter D. Brown (1)

1 Faculty of Life Sciences and Medicine
2 Faculty of Medicine and Health Sciences

► The paper examines the effects of a potential anti-diabetic drug glucokinase activator 50 (GKA50) on the function of insulin-secreting, pancreatic β-cells. ► GKA50 caused a sustained increase in β-cell volume, which was dependent on glucose metabolism. ► GKA50 stimulated a sustained depolarisation of the β-cell membrane potential by activating volume regulated anion channels (probably as a result of the increase in cell volume). ► The stimulatory effects of GKA50 on insulin secretion may at least partially be explained by cell swelling and activation of volume regulated anion channels leading to a depolarisation of membrane potential.

Mots clés: Vm; K channel; VRAC; NPPB; islets of Langerhans; pancreatic β-cell; cell volume; volume-regulated anion channel; glucokinase

Domaines: Biochimie, Biologie Moléculaire

Lisa Mcglasson, Len Best, Peter D. Brown. The glucokinase activator GKA50 causes an increase in cell volume and activation of volume-regulated anion channels in rat pancreatic β-cells. Molecular and Cellular Endocrinology, 2011, 342 (1-2), pp.48. ⟨10.1016/j.mce.2011.05.006⟩. ⟨hal-00721653⟩