Advanced

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

Li, Dai-Qing LU ; Jing, Xingjun LU ; Salehi, S Albert LU ; Collins, Stephan C; Hoppa, Michael B; Rosengren, Anders LU ; Zhang, Enming LU ; Lundquist, Ingmar LU ; Olofsson, Charlotta LU and Mörgelin, Matthias LU , et al. (2009) In Cell Metabolism 10(4). p.309-315
Abstract
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.... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Metabolism
volume
10
issue
4
pages
309 - 315
publisher
Cell Press
external identifiers
  • wos:000271086600010
  • pmid:19808023
  • scopus:70349632869
ISSN
1550-4131
DOI
10.1016/j.cmet.2009.08.011
language
English
LU publication?
yes
id
930a3545-4eb6-423e-8fe4-9d5565e1c038 (old id 1500600)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19808023?dopt=Abstract
date added to LUP
2009-11-04 09:43:26
date last changed
2017-07-02 04:36:09
@article{930a3545-4eb6-423e-8fe4-9d5565e1c038,
  abstract     = {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.},
  author       = {Li, Dai-Qing and Jing, Xingjun and Salehi, S Albert and Collins, Stephan C and Hoppa, Michael B and Rosengren, Anders and Zhang, Enming and Lundquist, Ingmar and Olofsson, Charlotta and Mörgelin, Matthias and Eliasson, Lena and Rorsman, Patrik and Renström, Erik},
  issn         = {1550-4131},
  language     = {eng},
  number       = {4},
  pages        = {309--315},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {Suppression of sulfonylurea- and glucose-induced insulin secretion in vitro and in vivo in mice lacking the chloride transport protein ClC-3.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2009.08.011},
  volume       = {10},
  year         = {2009},
}