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

Summary, in English

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: Sara Larsson; Nils Wierup; Frank Sundler; Lena Eliasson; Cecilia Holm
• Department/s: Molecular Endocrinology; Department of Experimental Medical Science; Diabetes - Islet Cell Exocytosis
• Publishing year: 2008
• Language: English
• Pages: 558-562
• Publication/Series: Biochemical and Biophysical Research Communications
• Volume: 376
• Links: http://www.ncbi.nlm.nih.gov/pubmed/18804448?dopt=Abstract; http://dx.doi.org/10.1016/j.bbrc.2008.09.045
• Document type: Journal article
• Publisher: Elsevier
• Topic: Biological Sciences
• Status: Published
• Research group: Molecular Endocrinology; Diabetes - Islet Cell Exocytosis
• ISBN/ISSN/Other: ISSN: 1090-2104