Lipases in the pancreatic beta-cell: implications for insulin secretion.
Fex, Malin LU and Mulder, Hindrik LU
(2008)
3rd Intracellular Proteolysis Meeting
In Biochemical Society Transactions
36(Pt 5).
p.885-890
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1285014
- author
- Fex, Malin
LU
and Mulder, Hindrik
LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- triacylglycerol, orlistat, lipolysis, islet, coupling signal, fatty acid
- in
- Biochemical Society Transactions
- volume
- 36
- issue
- Pt 5
- pages
- 885 - 890
- publisher
- Biochemical Society
- conference name
- 3rd Intracellular Proteolysis Meeting
- conference dates
- 2008-03-05 - 2008-03-07
- external identifiers
-
- wos:000260076300021
- pmid:18793156
- scopus:53849110273
- pmid:18793156
- ISSN
- 0300-5127
- DOI
- 10.1042/BST0360885
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Metabolism (013212001)
- id
- 3d726968-d965-4d0c-8a7d-03b2537cfdd4 (old id 1285014)
- date added to LUP
- 2016-04-01 11:53:04
- date last changed
- 2022-01-30 03:59:14
@article{3d726968-d965-4d0c-8a7d-03b2537cfdd4,
abstract = {{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.}},
author = {{Fex, Malin and Mulder, Hindrik}},
issn = {{0300-5127}},
keywords = {{triacylglycerol; orlistat; lipolysis; islet; coupling signal; fatty acid}},
language = {{eng}},
number = {{Pt 5}},
pages = {{885--890}},
publisher = {{Biochemical Society}},
series = {{Biochemical Society Transactions}},
title = {{Lipases in the pancreatic beta-cell: implications for insulin secretion.}},
url = {{http://dx.doi.org/10.1042/BST0360885}},
doi = {{10.1042/BST0360885}},
volume = {{36}},
year = {{2008}},
}