Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: Sulfonylurea-mediated stimulation of insulin exocytosis via an ATP-sensitive K+ channel-independent action.

Authors: Erik Renström, Sebastian Barg, Frank Thévenod, Patrik Rorsman

Journal, date & volume: Diabetes, 2002 Feb , 51 Suppl 1, S33-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11815455

Abstract
Several reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule pH is necessary for the insulin granule to gain release competence. Proton pumping into the granule is driven by a v-type H(+)-ATPase, but requires simultaneous Cl(-) uptake into the granule via metabolically regulated ClC-3 Cl(-) channels to maintain electroneutrality. Here we discuss the possibility that modulation of granule ClC-3 channels represents the mechanism whereby sulfonylureas directly potentiate the beta-cell exocytotic machinery.