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{beta}-Cell Lipases and Insulin Secretion.

Fex, Malin LU ; Lucas, Stephanie LU ; Sörhede Winzell, Maria LU ; Ahrén, Bo LU ; Holm, Cecilia LU and Mulder, Hindrik LU orcid (2006) In Diabetes 55(Suppl 2). p.24-31
Abstract
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... (More)
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. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATP-sensitive K+ channel, adipocyte triglyceride lipase, ATGL, FFA, free fatty acid, GSIS, HSL, glucose-stimulated insulin secretion, KATP channel, hormone-sensitive lipase
in
Diabetes
volume
55
issue
Suppl 2
pages
24 - 31
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000242602000005
  • scopus:33845528419
ISSN
1939-327X
DOI
10.2337/db06-S004
language
English
LU publication?
yes
id
3779a5f5-8d74-4a04-b094-209b079b458d (old id 164337)
date added to LUP
2016-04-01 16:08:28
date last changed
2021-08-04 03:22:20
@article{3779a5f5-8d74-4a04-b094-209b079b458d,
  abstract     = {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.},
  author       = {Fex, Malin and Lucas, Stephanie and Sörhede Winzell, Maria and Ahrén, Bo and Holm, Cecilia and Mulder, Hindrik},
  issn         = {1939-327X},
  language     = {eng},
  number       = {Suppl 2},
  pages        = {24--31},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {{beta}-Cell Lipases and Insulin Secretion.},
  url          = {http://dx.doi.org/10.2337/db06-S004},
  doi          = {10.2337/db06-S004},
  volume       = {55},
  year         = {2006},
}