Lack of cholesterol mobilization in islets of hormone-sensitive lipase deficient mice impairs insulin secretion.
Författare
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.
Avdelning/ar
Publiceringsår
2008
Språk
Engelska
Sidor
558-562
Publikation/Tidskrift/Serie
Biochemical and Biophysical Research Communications
Volym
376
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Biological Sciences
Status
Published
Forskningsgrupp
- Molecular Endocrinology
- Diabetes - Islet Cell Exocytosis
ISBN/ISSN/Övrigt
- ISSN: 1090-2104