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

First Author  Larsson S Year  2008
Journal  Biochem Biophys Res Commun Volume  376
Issue  3 Pages  558-62
PubMed ID  18804448 Mgi Jnum  J:142862
Mgi Id  MGI:3822273 Doi  10.1016/j.bbrc.2008.09.045
Citation  Larsson S, et al. (2008) Lack of cholesterol mobilization in islets of hormone-sensitive lipase deficient mice impairs insulin secretion. Biochem Biophys Res Commun 376(3):558-62
abstractText  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 25 kDa (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.
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