Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells

Détails

ID Serval
serval:BIB_C799305903FC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells
Périodique
Diabetologia
Auteur(s)
Martin  D., Allagnat  F., Chaffard  G., Caille  D., Fukuda  M., Regazzi  R., Abderrahmani  A., Waeber  G., Meda  P., Maechler  P., Haefliger  J. A.
ISSN
0012-186X
Statut éditorial
Publié
Date de publication
08/2008
Peer-reviewed
Oui
Volume
51
Numéro
8
Pages
1429-1439
Langue
anglais
Notes
Journal article --- Old month value: Apr 3, online publication date
Résumé
AIMS/HYPOTHESIS: The expression of several neuronal genes in pancreatic beta cells is due to the absence of the transcription factor repressor element 1 (RE-1) silencing transcription factor (REST). The identification of these traits and their functional significance in beta cells has only been partly elucidated. Herein, we investigated the biological consequences of a repression of REST target genes by expressing REST in beta cells. METHODS: The effect of REST expression on glucose homeostasis, insulin content and release, and beta cell mass was analysed in transgenic mice selectively expressing REST in beta cells. Relevant target genes were identified in INS-1E and primary beta cells expressing REST. RESULTS: Transgenic mice featuring a beta cell-targeted expression of REST exhibited glucose intolerance and reduced beta cell mass. In primary beta cells, REST repressed several proteins of the exocytotic machinery, including synaptosomal-associated protein (SNAP) 25, synaptotagmin (SYT) IV, SYT VII, SYT IX and complexin II; it impaired first and second phases of insulin secretion. Using RNA interference in INS-1E cells, we showed that SYT IV and SYT VII were implicated in the control of insulin release. CONCLUSIONS/INTERPRETATION: The data document the critical role of REST target genes in pancreatic beta cells. Specifically, we provide evidence that the downregulation of these genes is detrimental for the exocytosis of large dense core vesicles, thus contributing to beta cell dysfunction and impaired glucose homeostasis.
Mots-clé
Exocytosis, Insulin secretion, RE-1, RE-1 silencing transcription factor, REST, Synaptotagmins, Transgenic mice
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/05/2008 14:57
Dernière modification de la notice
09/05/2019 1:06
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