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Novel aspects of the molecular mechanisms controlling insulin secretion

Eliasson, Lena LU ; Abdulkader, Fernando; Braun, Matthias; Galvanovskis, Juris; Hoppa, Michael B. and Rorsman, Patrik (2008) In Journal of Physiology 586(14). p.3313-3324
Abstract
Pancreatic beta-cells secrete insulin by Ca2+-dependent exocytosis of secretory granules. beta-cell exocytosis involves SNARE (soluble NSF-attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L-type Ca2+ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in beta-cells in intact islets indicate a release rate of similar to 15 granules per beta-cell per second, 100-fold higher than that observed in biochemical assays. Single-vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule... (More)
Pancreatic beta-cells secrete insulin by Ca2+-dependent exocytosis of secretory granules. beta-cell exocytosis involves SNARE (soluble NSF-attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L-type Ca2+ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in beta-cells in intact islets indicate a release rate of similar to 15 granules per beta-cell per second, 100-fold higher than that observed in biochemical assays. Single-vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule lumen with the exterior is similar to 1.4 nm. This is considerably smaller than the size of insulin and membrane fusion is therefore not obligatorily associated with release of the cargo, a feature that may contribute to the different rates of secretion detected by the biochemical and biophysical measurements. However, small molecules like ATP and GABA, which are stored together with insulin in the granules, are small enough to be released via the narrow fusion pore, which accordingly functions as a molecular sieve. We finally consider the possibility that defective fusion pore expansion accounts for the decrease in insulin secretion observed in pathophysiological states including long-term exposure to lipids. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physiology
volume
586
issue
14
pages
3313 - 3324
publisher
The Physiological Society
external identifiers
  • wos:000257675800005
  • scopus:48949120517
ISSN
1469-7793
DOI
10.1113/jphysiol.2008.155317
language
English
LU publication?
yes
id
86a83d1f-489a-43ce-aa9a-155743f34837 (old id 1254653)
date added to LUP
2008-10-29 15:37:32
date last changed
2017-09-24 04:09:25
@article{86a83d1f-489a-43ce-aa9a-155743f34837,
  abstract     = {Pancreatic beta-cells secrete insulin by Ca2+-dependent exocytosis of secretory granules. beta-cell exocytosis involves SNARE (soluble NSF-attachment protein receptor) proteins similar to those controlling neurotransmitter release and depends on the close association of L-type Ca2+ channels and granules. In most cases, the secretory granules fuse individually but there is ultrastructural and biophysical evidence of multivesicular exocytosis. Estimates of the secretory rate in beta-cells in intact islets indicate a release rate of similar to 15 granules per beta-cell per second, 100-fold higher than that observed in biochemical assays. Single-vesicle capacitance measurements reveal that the diameter of the fusion pore connecting the granule lumen with the exterior is similar to 1.4 nm. This is considerably smaller than the size of insulin and membrane fusion is therefore not obligatorily associated with release of the cargo, a feature that may contribute to the different rates of secretion detected by the biochemical and biophysical measurements. However, small molecules like ATP and GABA, which are stored together with insulin in the granules, are small enough to be released via the narrow fusion pore, which accordingly functions as a molecular sieve. We finally consider the possibility that defective fusion pore expansion accounts for the decrease in insulin secretion observed in pathophysiological states including long-term exposure to lipids.},
  author       = {Eliasson, Lena and Abdulkader, Fernando and Braun, Matthias and Galvanovskis, Juris and Hoppa, Michael B. and Rorsman, Patrik},
  issn         = {1469-7793},
  language     = {eng},
  number       = {14},
  pages        = {3313--3324},
  publisher    = {The Physiological Society},
  series       = {Journal of Physiology},
  title        = {Novel aspects of the molecular mechanisms controlling insulin secretion},
  url          = {http://dx.doi.org/10.1113/jphysiol.2008.155317},
  volume       = {586},
  year         = {2008},
}