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ludc web

Lena Eliasson

Principal investigator

ludc web

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

Summary, in 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.

Department/s

  • Diabetes - Islet Patophysiology
  • Islet cell physiology
  • Department of Experimental Medical Science
  • Infection Medicine (BMC)
  • Diabetes - Islet Cell Exocytosis

Publishing year

2009

Language

English

Pages

309-315

Publication/Series

Cell Metabolism

Volume

10

Issue

4

Document type

Journal article

Publisher

Cell Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Islet cell physiology
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1550-4131