期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 376, 期 3, 页码 558-562出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2008.09.045
关键词
Insulin secretion; Hormone-sensitive lipase; Cholesterol; beta-cells; Methyl-beta-cyclodextrin
资金
- Swedish Research Council [112 84, 13147, 4499]
- European Union [LSHM-CT-2006-518153, LSHB-CT-2004-005137]
- Lund University Diabetes Center
- Swedish Diabetes Association
- Swedish medical association
- Novo Nordisk
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 (m beta cd). 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 m beta cd 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. (c) 2008 Elsevier Inc. All rights reserved
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