Cell Metab. 2009 Oct;10(4):316-23. doi: 10.1016/j.cmet.2009.08.012.

The granular chloride channel ClC-3 is permissive for insulin secretion.

Deriy LV, Gomez EA, Jacobson DA, Wang X, Hopson JA, Liu XY, Zhang G, Bindokas VP, Philipson LH, Nelson DJ.

Source

Department of Neurobiology, Pharmacology, and Physiology, The University of Chicago, Chicago, IL 60637, USA.

Abstract

Insulin secretion from pancreatic beta cells is dependent on maturation and acidification of the secretory granule, processes necessary for prohormone convertase cleavage of proinsulin. Previous studies in isolated beta cells revealed that acidification may be dependent on the granule membrane chloride channel ClC-3, in a step permissive for a regulated secretory response. In this study, immuno-EM of beta cells revealed colocalization of ClC-3 and insulin on secretory granules. Clcn3(-/-) mice as well as isolated islets demonstrate impaired insulin secretion; Clcn3(-/-) beta cells are defective in regulated insulin exocytosis and granular acidification. Increased amounts of proinsulin were found in the majority of secretory granules in the Clcn3(-/-) mice, while in Clcn3(+/+) cells, proinsulin was confined to the immature secretory granules. These results demonstrate that in pancreatic beta cells, chloride channels, specifically ClC-3, are localized on insulin granules and play a role in insulin processing as well as insulin secretion through regulation of granular acidification.

Comment in

ClC-3--a granular anion transporter involved in insulin secretion? [Cell Metab. 2010]
ClC-3--a granular anion transporter involved in insulin secretion?Jentsch TJ, Maritzen T, Keating DJ, Zdebik AA, Thévenod F. Cell Metab. 2010 Oct 6; 12(4):307-8; author reply 309-10.