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Lack of cholesterol mobilization in islets of hormone-sensitive lipase deficient mice impairs insulin secretion.

Larsson, Sara LU ; Wierup, Nils LU ; Sundler, Frank LU ; Eliasson, Lena LU and Holm, Cecilia LU (2008) In Biochemical and Biophysical Research Communications 376. p.558-562
Abstract
The observations that hormone-sensitive lipase (HSL) is located in close association to insulin granules in beta-cells and that cholesterol ester hydrolase activity is completely blunted in islets of HSL null mice made us hypothesize that the role of HSL in beta-cells is to provide cholesterol for the exocytosis of insulin. To test this hypothesis, wild type (wt) and HSL null islets were depleted of plasma membrane cholesterol using methyl-beta-cyclodextrin (mbetacd). A significant reduction in insulin secretion from HSL null islets was observed whereas wt islets were unaffected. Using synaptosomal protein of 25kDa (SNAP-25) as indicator of cholesterol-rich microdomains, confocal microscopy was used to show that HSL null beta-cells treated... (More)
The observations that hormone-sensitive lipase (HSL) is located in close association to insulin granules in beta-cells and that cholesterol ester hydrolase activity is completely blunted in islets of HSL null mice made us hypothesize that the role of HSL in beta-cells is to provide cholesterol for the exocytosis of insulin. To test this hypothesis, wild type (wt) and HSL null islets were depleted of plasma membrane cholesterol using methyl-beta-cyclodextrin (mbetacd). A significant reduction in insulin secretion from HSL null islets was observed whereas wt islets were unaffected. Using synaptosomal protein of 25kDa (SNAP-25) as indicator of cholesterol-rich microdomains, confocal microscopy was used to show that HSL null beta-cells treated with mbetacd contained fewer clusters than wt beta-cells. These results indicate that HSL plays an important role in insulin secretion by providing free cholesterol for the formation and maintenance of cholesterol-rich patches for docking of SNARE-proteins to the plasma membrane. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
376
pages
558 - 562
publisher
Elsevier
external identifiers
  • WOS:000260159000022
  • PMID:18804448
  • Scopus:53149125096
ISSN
1090-2104
DOI
10.1016/j.bbrc.2008.09.045
language
English
LU publication?
yes
id
2f287141-6c7a-418f-9395-4f0e8af20f19 (old id 1242848)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18804448?dopt=Abstract
date added to LUP
2008-10-03 17:23:27
date last changed
2016-10-13 04:31:28
@misc{2f287141-6c7a-418f-9395-4f0e8af20f19,
  abstract     = {The observations that hormone-sensitive lipase (HSL) is located in close association to insulin granules in beta-cells and that cholesterol ester hydrolase activity is completely blunted in islets of HSL null mice made us hypothesize that the role of HSL in beta-cells is to provide cholesterol for the exocytosis of insulin. To test this hypothesis, wild type (wt) and HSL null islets were depleted of plasma membrane cholesterol using methyl-beta-cyclodextrin (mbetacd). A significant reduction in insulin secretion from HSL null islets was observed whereas wt islets were unaffected. Using synaptosomal protein of 25kDa (SNAP-25) as indicator of cholesterol-rich microdomains, confocal microscopy was used to show that HSL null beta-cells treated with mbetacd contained fewer clusters than wt beta-cells. These results indicate that HSL plays an important role in insulin secretion by providing free cholesterol for the formation and maintenance of cholesterol-rich patches for docking of SNARE-proteins to the plasma membrane.},
  author       = {Larsson, Sara and Wierup, Nils and Sundler, Frank and Eliasson, Lena and Holm, Cecilia},
  issn         = {1090-2104},
  language     = {eng},
  pages        = {558--562},
  publisher    = {ARRAY(0x99d5198)},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Lack of cholesterol mobilization in islets of hormone-sensitive lipase deficient mice impairs insulin secretion.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2008.09.045},
  volume       = {376},
  year         = {2008},
}