Lund University is celebrating 350 years. Read more on lunduniversity.lu.se

Menu

Javascript is not activated in your browser. This website needs javascript activated to work properly.
You are here

Suppression of sulfonylurea- and glucose-induced insulin secretion in vitro and in vivo in mice lacking the chloride transport protein ClC-3.

Author:
  • Dai-Qing Li
  • Xingjun Jing
  • S Albert Salehi
  • Stephan C Collins
  • Michael B Hoppa
  • Anders Rosengren
  • Enming Zhang
  • Ingmar Lundquist
  • Charlotta Olofsson
  • Matthias Mörgelin
  • Lena Eliasson
  • Patrik Rorsman
  • Erik Renström
Publishing year: 2009
Language: English
Pages: 309-315
Publication/Series: Cell Metabolism
Volume: 10
Issue: 4
Document type: Journal article
Publisher: Cell Press

Abstract english

Priming of insulin secretory granules for release requires intragranular acidification and depends on vesicular Cl(-)-fluxes, but the identity of the chloride transporter/ion channel involved is unknown. We tested the hypothesis that the chloride transport protein ClC-3 fulfills these actions in pancreatic beta cells. In ClC-3(-/-) mice, insulin secretion evoked by membrane depolarization (high extracellular K(+), sulfonylureas), or glucose was >60% reduced compared to WT animals. This effect was mirrored by a approximately 80% reduction in depolarization-evoked beta cell exocytosis (monitored as increases in cell capacitance) in single ClC-3(-/-) beta cells, as well as a 44% reduction in proton transport across the granule membrane. ClC-3 expression in the insulin granule was demonstrated by immunoblotting, immunostaining, and negative immuno-EM in a high-purification fraction of large dense-core vesicles (LDCVs) obtained by phogrin-EGFP labeling. The data establish the importance of granular Cl(-) fluxes in granule priming and provide direct evidence for the involvement of ClC-3 in the process.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Islet patophysiology
  • Islet cell physiology
  • Islet cell exocytosis
  • ISSN: 1550-4131
Erik Renström
E-mail: erik [dot] renstrom [at] med [dot] lu [dot] se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

33

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00