Lipids have been implicated in β-cell stimulus–secretion coupling. In such a role, lipases in β-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 β-cell lipase(s), we found that HSL (hormone-sensitive lipase), the rate-limiting enzyme for acylglycerol hydrolysis in adipocytes, is expressed in rodent β-cells. To resolve the role of this lipase, we have created global and β-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, β-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 β-cell stimulus–secretion coupling.
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Conference Article|
September 19 2008
Lipases in the pancreatic β-cell: implications for insulin secretion
Malin Fex;
Malin Fex
*Units of Diabetes and Celiac Disease, Lund University Diabetes Centre, Malmö University Hospital, Malmö, SE-205 02, Sweden
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Hindrik Mulder
Hindrik Mulder
1
†Unit of Molecular Metabolism, Lund University Diabetes Centre, Malmö University Hospital, Malmö, SE-205 02, Sweden
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
June 26 2008
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (5): 885–890.
Article history
Received:
June 26 2008
Citation
Malin Fex, Hindrik Mulder; Lipases in the pancreatic β-cell: implications for insulin secretion. Biochem Soc Trans 1 October 2008; 36 (5): 885–890. doi: https://doi.org/10.1042/BST0360885
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