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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)
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author
organization
publishing date
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
external identifiers
  • WOS:000260076300021
  • PMID:18793156
  • Scopus:53849110273
ISSN
0300-5127
DOI
10.1042/BST0360885
language
English
LU publication?
yes
id
3d726968-d965-4d0c-8a7d-03b2537cfdd4 (old id 1285014)
date added to LUP
2008-10-07 14:22:33
date last changed
2016-10-13 05:09:55
@misc{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},
  keyword      = {triacylglycerol,orlistat,lipolysis,islet,coupling signal,fatty acid},
  language     = {eng},
  number       = {Pt 5},
  pages        = {885--890},
  publisher    = {ARRAY(0x961d160)},
  series       = {Biochemical Society Transactions},
  title        = {Lipases in the pancreatic beta-cell: implications for insulin secretion.},
  url          = {http://dx.doi.org/10.1042/BST0360885},
  volume       = {36},
  year         = {2008},
}