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Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion.

Mulder, Hindrik LU ; Yang, Shumin; Sörhede Winzell, Maria LU ; Holm, Cecilia LU and Ahrén, Bo LU (2004) In Diabetes 53(1). p.122-128
Abstract
Lipids may serve as coupling factors in KATP-independent glucose sensing in β-cells. We have previously demonstrated that β-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether β-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an... (More)
Lipids may serve as coupling factors in KATP-independent glucose sensing in β-cells. We have previously demonstrated that β-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether β-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an acylglyceride-derived coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS, an effect proposed to be due to activation of a lipase. In perifused islets, orlistat attenuated mainly the second phase of insulin secretion. Because the rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar were unaffected by orlistat whereas the second phase of insulin secretion was reduced, it seems likely that a lipid coupling factor involved in KATP-independent glucose sensing has been perturbed. Thus, β-cell lipase activity is involved in GSIS, emphasizing the important role of β-cell lipid metabolism for insulin secretion. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
53
issue
1
pages
122 - 128
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000187632400017
  • pmid:14693706
  • scopus:0347360366
ISSN
1939-327X
DOI
10.2337/diabetes.53.1.122
language
English
LU publication?
yes
id
b31753a6-6992-4d91-8f61-c3ae1521094d (old id 119392)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14693706&dopt=Abstract
date added to LUP
2007-06-29 14:27:44
date last changed
2017-03-12 04:06:33
@article{b31753a6-6992-4d91-8f61-c3ae1521094d,
  abstract     = {Lipids may serve as coupling factors in KATP-independent glucose sensing in β-cells. We have previously demonstrated that β-cells harbor lipase activities, one of which is the hormone-sensitive lipase. Whether β-cell lipases are critical for glucose-stimulated insulin secretion (GSIS) by providing lipid-derived signals from endogenous lipids is unknown. Therefore, using a lipase inhibitor (orlistat), we examined whether lipase inhibition reduces insulin secretion. Islet lipolysis stimulated by glucose and diglyceride lipase activity was abolished by orlistat. Incubation of rat islets with orlistat dose dependently inhibited GSIS; this inhibition was reversed by 1 mmol/l palmitate, suggesting that orlistat acts via impaired formation of an acylglyceride-derived coupling signal. Orlistat inhibited the potentiating effect of forskolin on GSIS, an effect proposed to be due to activation of a lipase. In perifused islets, orlistat attenuated mainly the second phase of insulin secretion. Because the rise in islet ATP/ADP levels in response to glucose and oxidation of the sugar were unaffected by orlistat whereas the second phase of insulin secretion was reduced, it seems likely that a lipid coupling factor involved in KATP-independent glucose sensing has been perturbed. Thus, β-cell lipase activity is involved in GSIS, emphasizing the important role of β-cell lipid metabolism for insulin secretion.},
  author       = {Mulder, Hindrik and Yang, Shumin and Sörhede Winzell, Maria and Holm, Cecilia and Ahrén, Bo},
  issn         = {1939-327X},
  language     = {eng},
  number       = {1},
  pages        = {122--128},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Inhibition of lipase activity and lipolysis in rat islets reduces insulin secretion.},
  url          = {http://dx.doi.org/10.2337/diabetes.53.1.122},
  volume       = {53},
  year         = {2004},
}