A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells.

Détails

Ressource 1Télécharger: BIB_093D5FE7BBC7.P001.pdf (5629.81 [Ko])
Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_093D5FE7BBC7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells.
Périodique
Plos One
Auteur(s)
Cigliola V., Populaire C., Pierri C.L., Deutsch S., Haefliger J.A., Fadista J., Lyssenko V., Groop L., Rueedi R., Thorel F., Herrera P.L., Meda P.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
11
Numéro
3
Pages
e0150880
Langue
anglais
Résumé
Signalling through gap junctions contributes to control insulin secretion and, thus, blood glucose levels. Gap junctions of the insulin-producing β-cells are made of connexin 36 (Cx36), which is encoded by the GJD2 gene. Cx36-null mice feature alterations mimicking those observed in type 2 diabetes (T2D). GJD2 is also expressed in neurons, which share a number of common features with pancreatic β-cells. Given that a synonymous exonic single nucleotide polymorphism of human Cx36 (SNP rs3743123) associates with altered function of central neurons in a subset of epileptic patients, we investigated whether this SNP also caused alterations of β-cell function. Transfection of rs3743123 cDNA in connexin-lacking HeLa cells resulted in altered formation of gap junction plaques and cell coupling, as compared to those induced by wild type (WT) GJD2 cDNA. Transgenic mice expressing the very same cDNAs under an insulin promoter revealed that SNP rs3743123 expression consistently lead to a post-natal reduction of islet Cx36 levels and β-cell survival, resulting in hyperglycemia in selected lines. These changes were not observed in sex- and age-matched controls expressing WT hCx36. The variant GJD2 only marginally associated to heterogeneous populations of diabetic patients. The data document that a silent polymorphism of GJD2 is associated with altered β-cell function, presumably contributing to T2D pathogenesis.
Pubmed
Web of science
Création de la notice
10/03/2016 18:57
Dernière modification de la notice
03/03/2018 13:31
Données d'usage