Titre
A role for the malonyl-CoA/long-chain acyl-CoA pathway of lipid signaling in the regulation of insulin secretion in response to both fuel and nonfuel stimuli.
Type
article
Institution
Externe
Périodique
Auteur(s)
Roduit, R.
Auteure/Auteur
Nolan, C.
Auteure/Auteur
Alarcon, C.
Auteure/Auteur
Moore, P.
Auteure/Auteur
Barbeau, A.
Auteure/Auteur
Delghingaro-Augusto, V.
Auteure/Auteur
Przybykowski, E.
Auteure/Auteur
Morin, J.
Auteure/Auteur
Massé, F.
Auteure/Auteur
Massie, B.
Auteure/Auteur
Ruderman, N.
Auteure/Auteur
Rhodes, C.
Auteure/Auteur
Poitout, V.
Auteure/Auteur
Prentki, M.
Auteure/Auteur
Liens vers les personnes
ISSN
0012-1797
Statut éditorial
Publié
Date de publication
2004-04
Volume
53
Numéro
4
Première page
1007
Dernière page/numéro d’article
1019
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Résumé
The malonyl-CoA/long-chain acyl-CoA (LC-CoA) model of glucose-induced insulin secretion (GIIS) predicts that malonyl-CoA derived from glucose metabolism inhibits fatty acid oxidation, thereby increasing the availability of LC-CoA for lipid signaling to cellular processes involved in exocytosis. For directly testing the model, INSr3 cell clones overexpressing malonyl-CoA decarboxylase in the cytosol (MCDc) in a tetracycline regulatable manner were generated, and INS(832/13) and rat islets were infected with MCDc-expressing adenoviruses. MCD activity was increased more than fivefold, and the malonyl-CoA content was markedly diminished. This was associated with enhanced fat oxidation at high glucose, a suppression of the glucose-induced increase in cellular free fatty acid (FFA) content, and reduced partitioning at elevated glucose of exogenous palmitate into lipid esterification products. MCDc overexpression, in the presence of exogenous FFAs but not in their absence, reduced GIIS in all beta-cell lines and in rat islets. It also markedly curtailed the stimulation of insulin secretion by other fuel and nonfuel secretagogues. In the absence of MCDc overexpression, the secretory responses to all types of secretagogues were amplified by the provision of exogenous fatty acids. In the presence of exogenous FFAs, the fatty acyl-CoA synthetase inhibitor triacsin C reduced secretion in response to glucose and nonfuel stimuli. The data show the existence of important links between the metabolic coupling factor malonyl-CoA, the partitioning of fatty acids, and the stimulation of insulin secretion to both fuel and nonfuel stimuli.
Sujets
PID Serval
serval:BIB_55AB112846A9
PMID
Open Access
Oui
Date de création
2017-09-15T11:13:42.869Z
Date de création dans IRIS
2025-05-20T14:39:33Z