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Sulfonylurea-Mediated Stimulation of Insulin Exocytosis via an ATP-Sensitive K(+) Channel--Independent Action.

Renström, Erik LU ; Barg, Sebastian LU ; Thévenod, Frank and Rorsman, Patrik LU (2002) In Diabetes 51(Suppl 1). p.33-36
Abstract
Several reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule pH is necessary for the insulin granule to gain release competence. Proton pumping into the granule is driven by a v-type H(+)-ATPase, but requires simultaneous Cl(-) uptake into the granule via metabolically regulated ClC-3 Cl(-) channels to maintain electroneutrality. Here we discuss the possibility that modulation of granule ClC-3 channels represents the mechanism whereby sulfonylureas directly potentiate the beta-cell exocytotic machinery.
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
51
issue
Suppl 1
pages
33 - 36
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000173599900007
  • scopus:0036311172
ISSN
1939-327X
DOI
10.2337/diabetes.51.2007.S33
language
English
LU publication?
yes
id
7536508a-33e7-486e-a96a-709f41345fca (old id 106393)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11815455&dopt=Abstract
date added to LUP
2007-07-19 08:56:21
date last changed
2017-11-12 03:55:32
@article{7536508a-33e7-486e-a96a-709f41345fca,
  abstract     = {Several reports indicate that hypoglycemic sulfonylureas augment Ca(2+)-dependent insulin secretion via mechanisms other than inhibition of the ATP-sensitive K(+) channel. The effect involves a 65-kd protein in the granule membrane and culminates in intragranular acidification. Lowering of granule pH is necessary for the insulin granule to gain release competence. Proton pumping into the granule is driven by a v-type H(+)-ATPase, but requires simultaneous Cl(-) uptake into the granule via metabolically regulated ClC-3 Cl(-) channels to maintain electroneutrality. Here we discuss the possibility that modulation of granule ClC-3 channels represents the mechanism whereby sulfonylureas directly potentiate the beta-cell exocytotic machinery.},
  author       = {Renström, Erik and Barg, Sebastian and Thévenod, Frank and Rorsman, Patrik},
  issn         = {1939-327X},
  language     = {eng},
  number       = {Suppl 1},
  pages        = {33--36},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Sulfonylurea-Mediated Stimulation of Insulin Exocytosis via an ATP-Sensitive K(+) Channel--Independent Action.},
  url          = {http://dx.doi.org/10.2337/diabetes.51.2007.S33},
  volume       = {51},
  year         = {2002},
}