Contribution of Intronic miR-338-3p and Its Hosting Gene AATK to Compensatory β-Cell Mass Expansion.

Détails

Ressource 1Télécharger: BIB_912547987857.P001.pdf (2151.93 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_912547987857
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Contribution of Intronic miR-338-3p and Its Hosting Gene AATK to Compensatory β-Cell Mass Expansion.
Périodique
Molecular Endocrinology
Auteur(s)
Jacovetti C., Jimenez V., Ayuso E., Laybutt R., Peyot M.L., Prentki M., Bosch F., Regazzi R.
ISSN
1944-9917 (Electronic)
ISSN-L
0888-8809
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
29
Numéro
5
Pages
693-702
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
The elucidation of the mechanisms directing β-cell mass regeneration and maintenance is of interest, because the deficit of β-cell mass contributes to diabetes onset and progression. We previously found that the level of the microRNA (miRNA) miR-338-3p is decreased in pancreatic islets from rodent models displaying insulin resistance and compensatory β-cell mass expansion, including pregnant rats, diet-induced obese mice, and db/db mice. Transfection of rat islet cells with oligonucleotides that specifically block miR-338-3p activity increased the fraction of proliferating β-cells in vitro and promoted survival under proapoptotic conditions without affecting the capacity of β-cells to release insulin in response to glucose. Here, we evaluated the role of miR-338-3p in vivo by injecting mice with an adeno-associated viral vector permitting specific sequestration of this miRNA in β-cells. We found that the adeno-associated viral construct increased the fraction of proliferating β-cells confirming the data obtained in vitro. miR-338-3p is generated from an intron of the gene coding for apoptosis-associated tyrosine kinase (AATK). Similarly to miR-338-3p, we found that AATK is down-regulated in rat and human islets and INS832/13 β-cells in the presence of the cAMP-raising agents exendin-4, estradiol, and a G-protein-coupled Receptor 30 agonist. Moreover, AATK expression is reduced in islets of insulin resistant animal models and selective silencing of AATK in INS832/13 cells by RNA interference promoted β-cell proliferation. The results point to a coordinated reduction of miR-338-3p and AATK under insulin resistance conditions and provide evidence for a cooperative action of the miRNA and its hosting gene in compensatory β-cell mass expansion.
Pubmed
Web of science
Création de la notice
10/06/2015 7:52
Dernière modification de la notice
03/03/2018 19:27
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