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PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells

Eliasson, Lena ; Renström, Erik LU ; Ammala, Carina ; Berggren, Per-Olof ; Bertorello, Alejandro M. ; Bokvist, Krister ; Chibalin, Alexander ; Deeney, Jude T. ; Flatt, Peter R. and Gabel, Jakob , et al. (1996) In Science 271(5250). p.813-815
Abstract
Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which... (More)
Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science
volume
271
issue
5250
pages
813 - 815
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:8628999
  • scopus:13344269671
ISSN
1095-9203
DOI
10.1126/science.271.5250.813
language
English
LU publication?
yes
id
fb786f9b-4b04-460f-b94b-bdb528300381 (old id 1109849)
date added to LUP
2016-04-01 16:47:43
date last changed
2022-03-15 03:00:41
@article{fb786f9b-4b04-460f-b94b-bdb528300381,
  abstract     = {{Hypoglycemic sulfonylureas represent a group of clinically useful antidiabetic compounds that stimulate insulin secretion from pancreatic beta cells. The molecular mechanisms involved are not fully understood but are believed to involve inhibition of potassium channels sensitive to adenosine triphosphate (KATP channels) in the beta cell membrane, causing membrane depolarization, calcium influx, and activation of the secretory machinery. In addition to these effects, sulfonylureas also promoted exocytosis by direct interaction with the secretory machinery not involving closure of the plasma membrane KATP channels. This effect was dependent on protein kinase C (PKC) and was observed at therapeutic concentrations of sulfonylureas, which suggests that it contributes to their hypoglycemic action in diabetics.}},
  author       = {{Eliasson, Lena and Renström, Erik and Ammala, Carina and Berggren, Per-Olof and Bertorello, Alejandro M. and Bokvist, Krister and Chibalin, Alexander and Deeney, Jude T. and Flatt, Peter R. and Gabel, Jakob and Gromada, Jesper and Larsson, Olof and Lindstrom, Per and Rhodes, Christopher J. and Rorsman, Patrik}},
  issn         = {{1095-9203}},
  language     = {{eng}},
  number       = {{5250}},
  pages        = {{813--815}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science}},
  title        = {{PKC-dependent stimulation of exocytosis by sulfonylureas in pancreatic beta cells}},
  url          = {{http://dx.doi.org/10.1126/science.271.5250.813}},
  doi          = {{10.1126/science.271.5250.813}},
  volume       = {{271}},
  year         = {{1996}},
}