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Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol.

Vikman, Jenny LU ; Jimenez, Javier LU ; Nyman, Per; Thelin, Johan and Eliasson, Lena (2009) In The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23(1). p.58-67
Abstract
Cholesterol-rich clusters of SNARE (soluble NSF attachment protein receptor) proteins have been implicated as being important for exocytosis. Here we demonstrate the significance of cholesterol for normal biphasic insulin secretion in mouse beta cells by removal of cholesterol from the plasma membrane using methyl-beta-cyclodextrin (MBCD). Maximal inhibition of insulin secretion in static incubations was achieved using 0.1 mM MBCD. In in situ pancreatic perfusion measurements, both first and second phase insulin secretions were reduced by approximately 50% (P<0.05). This was accompanied by a reduced number of docked large dense core vesicles (LDCVs) ( approximately 40%; P<0.01) and a reduced exocytotic response (>50%; P<0.01).... (More)
Cholesterol-rich clusters of SNARE (soluble NSF attachment protein receptor) proteins have been implicated as being important for exocytosis. Here we demonstrate the significance of cholesterol for normal biphasic insulin secretion in mouse beta cells by removal of cholesterol from the plasma membrane using methyl-beta-cyclodextrin (MBCD). Maximal inhibition of insulin secretion in static incubations was achieved using 0.1 mM MBCD. In in situ pancreatic perfusion measurements, both first and second phase insulin secretions were reduced by approximately 50% (P<0.05). This was accompanied by a reduced number of docked large dense core vesicles (LDCVs) ( approximately 40%; P<0.01) and a reduced exocytotic response (>50%; P<0.01). Further, subcellular fractionations demonstrated movement of the synaptosomal protein of 25 kDa (SNAP-25) from the plasma membrane to the cytosol after MBCD treatment. The inhibitory actions of MBCD were counteracted by subsequent addition of cholesterol. We hypothesize that desorption of cholesterol leads to the disturbance of a basic exocytotic mechanism partly due to migration of SNAP-25, and we conclude that insulin secretion is highly sensitive to changes in plasma membrane cholesterol.-Vikman, J., Jimenez-Feltström, J., Nyman, P., Thelin, J., Eliasson, L. Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
volume
23
issue
1
pages
58 - 67
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • wos:000262095500008
  • pmid:18806218
  • scopus:58249094871
ISSN
1530-6860
DOI
10.1096/fj.08-105734
language
English
LU publication?
yes
id
6464fa5e-cbf7-436d-b8e0-cb03d2d66750 (old id 1242808)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18806218?dopt=Abstract
date added to LUP
2008-10-03 17:00:19
date last changed
2017-06-25 04:38:29
@article{6464fa5e-cbf7-436d-b8e0-cb03d2d66750,
  abstract     = {Cholesterol-rich clusters of SNARE (soluble NSF attachment protein receptor) proteins have been implicated as being important for exocytosis. Here we demonstrate the significance of cholesterol for normal biphasic insulin secretion in mouse beta cells by removal of cholesterol from the plasma membrane using methyl-beta-cyclodextrin (MBCD). Maximal inhibition of insulin secretion in static incubations was achieved using 0.1 mM MBCD. In in situ pancreatic perfusion measurements, both first and second phase insulin secretions were reduced by approximately 50% (P&lt;0.05). This was accompanied by a reduced number of docked large dense core vesicles (LDCVs) ( approximately 40%; P&lt;0.01) and a reduced exocytotic response (&gt;50%; P&lt;0.01). Further, subcellular fractionations demonstrated movement of the synaptosomal protein of 25 kDa (SNAP-25) from the plasma membrane to the cytosol after MBCD treatment. The inhibitory actions of MBCD were counteracted by subsequent addition of cholesterol. We hypothesize that desorption of cholesterol leads to the disturbance of a basic exocytotic mechanism partly due to migration of SNAP-25, and we conclude that insulin secretion is highly sensitive to changes in plasma membrane cholesterol.-Vikman, J., Jimenez-Feltström, J., Nyman, P., Thelin, J., Eliasson, L. Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol.},
  author       = {Vikman, Jenny and Jimenez, Javier and Nyman, Per and Thelin, Johan and Eliasson, Lena},
  issn         = {1530-6860},
  language     = {eng},
  number       = {1},
  pages        = {58--67},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {The FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
  title        = {Insulin secretion is highly sensitive to desorption of plasma membrane cholesterol.},
  url          = {http://dx.doi.org/10.1096/fj.08-105734},
  volume       = {23},
  year         = {2009},
}