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Mechanisms of exocytosis in insulin-secreting B-cells and glucagon-secreting A-cells.

Barg, Sebastian LU (2003) In Pharmacology and Toxicology1987-01-01+01:002004-01-01+01:00 92(1). p.3-13
Abstract
In pancreatic B- and A-cells, metabolic stimuli regulate biochemical and electrical processes that culminate in Ca2+-influx and release of insulin or glucagon, respectively. Like in other (neuro)endocrine cells, Ca2+-influx triggers the rapid exocytosis of hormone-containing secretory granules. Only a small fraction of granules (<1% in insulin-secreting B-cells) can be released immediately, while the remainder requires translocation to the plasma membrane and further "priming" for release by several ATP- and Ca2+-dependent reactions. Such functional organization may account for systemic features such as the biphasic time course of glucose-stimulated insulin secretion. Since this release pattern is altered in type-2 diabetes mellitus, it... (More)
In pancreatic B- and A-cells, metabolic stimuli regulate biochemical and electrical processes that culminate in Ca2+-influx and release of insulin or glucagon, respectively. Like in other (neuro)endocrine cells, Ca2+-influx triggers the rapid exocytosis of hormone-containing secretory granules. Only a small fraction of granules (<1% in insulin-secreting B-cells) can be released immediately, while the remainder requires translocation to the plasma membrane and further "priming" for release by several ATP- and Ca2+-dependent reactions. Such functional organization may account for systemic features such as the biphasic time course of glucose-stimulated insulin secretion. Since this release pattern is altered in type-2 diabetes mellitus, it is conceivable that disturbances in the exocytotic machinery underlie the disease. Here I will review recent data from our laboratory relevant for the understanding of these processes in insulin-secreting B-cells and glucagon-secreting A-cells and for the identification of novel targets for antidiabetic drug action. Two aspects are discussed in detail: 1) The importance of a tight interaction between L-type Ca2+-channels and the exocytotic machinery for efficient secretion; and 2) the role of intragranular acidification for the priming of secretory granules and its regulation by a granular 65-kDa sulfonylurea-binding protein. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacology and Toxicology1987-01-01+01:002004-01-01+01:00
volume
92
issue
1
pages
3 - 13
publisher
Wiley-Blackwell
external identifiers
  • pmid:12710591
  • wos:000180963600002
  • scopus:0037284341
ISSN
1600-0773
DOI
10.1034/j.1600-0773.2003.920102.x
language
English
LU publication?
yes
id
76224da7-e01f-4f64-bba1-2fb8f1ce51ac (old id 113197)
date added to LUP
2007-07-10 10:03:02
date last changed
2018-01-07 06:10:12
@article{76224da7-e01f-4f64-bba1-2fb8f1ce51ac,
  abstract     = {In pancreatic B- and A-cells, metabolic stimuli regulate biochemical and electrical processes that culminate in Ca2+-influx and release of insulin or glucagon, respectively. Like in other (neuro)endocrine cells, Ca2+-influx triggers the rapid exocytosis of hormone-containing secretory granules. Only a small fraction of granules (&lt;1% in insulin-secreting B-cells) can be released immediately, while the remainder requires translocation to the plasma membrane and further "priming" for release by several ATP- and Ca2+-dependent reactions. Such functional organization may account for systemic features such as the biphasic time course of glucose-stimulated insulin secretion. Since this release pattern is altered in type-2 diabetes mellitus, it is conceivable that disturbances in the exocytotic machinery underlie the disease. Here I will review recent data from our laboratory relevant for the understanding of these processes in insulin-secreting B-cells and glucagon-secreting A-cells and for the identification of novel targets for antidiabetic drug action. Two aspects are discussed in detail: 1) The importance of a tight interaction between L-type Ca2+-channels and the exocytotic machinery for efficient secretion; and 2) the role of intragranular acidification for the priming of secretory granules and its regulation by a granular 65-kDa sulfonylurea-binding protein.},
  author       = {Barg, Sebastian},
  issn         = {1600-0773},
  language     = {eng},
  number       = {1},
  pages        = {3--13},
  publisher    = {Wiley-Blackwell},
  series       = {Pharmacology and Toxicology1987-01-01+01:002004-01-01+01:00},
  title        = {Mechanisms of exocytosis in insulin-secreting B-cells and glucagon-secreting A-cells.},
  url          = {http://dx.doi.org/10.1034/j.1600-0773.2003.920102.x},
  volume       = {92},
  year         = {2003},
}