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. |