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Cecilia Holm

Professor

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

Author

  • Sara Larsson
  • Nils Wierup
  • Frank Sundler
  • Lena Eliasson
  • Cecilia Holm

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.

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

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