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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1242848
- author
- Larsson, Sara
LU
; Wierup, Nils
LU
; Sundler, Frank
LU
; Eliasson, Lena
LU
and Holm, Cecilia
LU
- organization
- publishing date
- 2008
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Endocrinology (013212018), Neuroendocrine Cell Biology (013212008), Islet cell exocytosis (013212135)
- 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
- 2016-04-04 09:29:14
- date last changed
- 2022-01-29 18:05:35
@article{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 = {{Elsevier}},
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}},
doi = {{10.1016/j.bbrc.2008.09.045}},
volume = {{376}},
year = {{2008}},
}