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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Lipases in the pancreatic beta-cell: implications for insulin secretion.

Author

  • Malin Fex
  • Hindrik Mulder

Summary, in English

Lipids have been implicated in beta-cell stimulus-secretion coupling. In such a role, lipases in beta-cells would be required to generate lipid coupling factors. We have shown previously that glucose stimulates lipolysis in rodent islets. In addition, lipolysis and diacylglycerol lipase activity in islets are abolished by orlistat, an irreversible lipase inhibitor with a broad specificity for substrates. Moreover, orlistat dose-dependently inhibits glucose- and forskolin-stimulated insulin secretion, while leaving glucose oxidation and the rise in the ATP/ADP ratio intact. In an effort to identify beta-cell lipase(s), we found that HSL (hormone-sensitive lipase), the rate-limiting enzyme for acylglycerol hydrolysis in adipocytes, is expressed in rodent beta-cells. To resolve the role of this lipase, we have created global and beta-cell-specific knockout mice. Although our line of global HSL-knockout mice is moderately glucose-intolerant owing to reduced peripheral insulin sensitivity and exhibits normal islet metabolism and insulin secretion, other HSL-knockout lines have displayed impaired insulin secretion under certain conditions. In contrast, beta-cell-specific HSL-knockout mice, which are less prone to genetic redundancy, are hyperglycaemic, presumably caused by a perturbation of first-phase insulin secretion. Thus studies by us and others demonstrate that lipases, such as HSL, play a regulatory role in beta-cell stimulus-secretion coupling.

Department/s

  • Diabetes and Celiac Unit
  • Department of Experimental Medical Science

Publishing year

2008

Language

English

Pages

885-890

Publication/Series

Biochemical Society Transactions

Volume

36

Issue

Pt 5

Document type

Journal article

Publisher

Biochemical Society

Topic

  • Biochemistry and Molecular Biology

Keywords

  • triacylglycerol
  • orlistat
  • lipolysis
  • islet
  • coupling signal
  • fatty acid

Conference name

3rd Intracellular Proteolysis Meeting

Conference date

2008-03-05 - 2008-03-07

Status

Published

Research group

  • Diabetes and Celiac Unit

ISBN/ISSN/Other

  • ISSN: 0300-5127