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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1254653
- author
- Eliasson, Lena
LU
; Abdulkader, Fernando
; Braun, Matthias
; Galvanovskis, Juris
; Hoppa, Michael B.
and Rorsman, Patrik
- organization
- publishing date
- 2008
- 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
- pmid:18511483
- 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
- 2016-04-01 14:32:21
- date last changed
- 2022-04-22 03:46:33
@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}},
doi = {{10.1113/jphysiol.2008.155317}},
volume = {{586}},
year = {{2008}},
}