Mechanisms of exocytosis in insulin-secreting B-cells and glucagon-secreting A-cells.
(2003) In Pharmacology and Toxicology 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/113197
- author
- Barg, Sebastian LU
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Pharmacology and Toxicology
- 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
- 2016-04-01 12:24:34
- date last changed
- 2022-02-18 22:06:00
@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 (<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 Toxicology}},
title = {{Mechanisms of exocytosis in insulin-secreting B-cells and glucagon-secreting A-cells.}},
url = {{https://lup.lub.lu.se/search/files/2911373/623730.pdf}},
doi = {{10.1034/j.1600-0773.2003.920102.x}},
volume = {{92}},
year = {{2003}},
}