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:
https://lup.lub.lu.se/record/1500600
- author
- 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. (More)
- 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
; Mörgelin, Matthias
LU
; Eliasson, Lena
LU
; Rorsman, Patrik
LU
and Renström, Erik
LU
(Less)
- organization
- publishing date
- 2009
- 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
- pmid:19808023
- 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
- 2016-04-04 08:55:53
- date last changed
- 2022-01-29 07:50:25
@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 = {{https://lup.lub.lu.se/search/files/5213208/1512593.pdf}},
doi = {{10.1016/j.cmet.2009.08.011}},
volume = {{10}},
year = {{2009}},
}