Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Cecilia Holm

Professor

Default user image.

{beta}-Cell Lipases and Insulin Secretion.

Author

  • Malin Fex
  • Stephanie Lucas
  • Maria Sörhede Winzell
  • Bo Ahrén
  • Cecilia Holm
  • Hindrik Mulder

Summary, in English

Lipids have been implicated in ß-cell stimulus-secretion coupling. Thus, lipases in ß-cells would be required to generate coupling factors from intracellular lipids. Indeed, we found that glucose stimulates lipolysis in rodent islets and clonal ß-cells. Lipolysis and diglyceride lipase activity in islets are abolished by orlistat, a pan-lipase inhibitor. Moreover, orlistat dose-dependently inhibits glucose- and forskolin-stimulated insulin secretion, while leaving glucose oxidation and the rise in ATP-to-ADP ratio intact. In an effort to identify ß-cell lipase(s), we found that hormone-sensitive lipase (HSL), the rate-limiting enzyme for acylglyceride hydrolysis in adipocytes, is active in rodent ß-cells. To further address the role of HSL, a global and ß-cell–specific inactivation, respectively, of the lipase has been created in mice. Whereas our line of HSL null mice is moderately glucose intolerant due to reduced peripheral insulin sensitivity, it exhibits normal islet metabolism and insulin secretion. Preliminary analysis of the ß-cell–specific HSL knockout has revealed no evidence for disturbed islet function. Thus, studies of ours and others indicate that there is a complex lipid regulatory component in ß-cell stimulus-secretion coupling. The role of HSL and other lipases needs to be further clarified to provide a balanced view of the role of lipids and lipolysis in ß-cells.

Department/s

  • Diabetes and Celiac Unit
  • Molecular Endocrinology
  • Medicine, Lund
  • Diabetes - Molecular Metabolism

Publishing year

2006

Language

English

Pages

24-31

Publication/Series

Diabetes

Volume

55

Issue

Suppl 2

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Keywords

  • ATP-sensitive K+ channel
  • adipocyte triglyceride lipase
  • ATGL
  • FFA
  • free fatty acid
  • GSIS
  • HSL
  • glucose-stimulated insulin secretion
  • KATP channel
  • hormone-sensitive lipase

Status

Published

Research group

  • Diabetes and Celiac Unit
  • Molecular Endocrinology
  • Diabetes - Molecular Metabolism

ISBN/ISSN/Other

  • ISSN: 1939-327X