Hyperglycemia downregulates Connexin36 in pancreatic islets via the upregulation of ICER-1/ICER-1γ.

Détails

ID Serval
serval:BIB_3E35AE378448
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hyperglycemia downregulates Connexin36 in pancreatic islets via the upregulation of ICER-1/ICER-1γ.
Périodique
Journal of Molecular Endocrinology
Auteur(s)
Haefliger J.A., Rohner-Jeanrenaud F., Caille D., Charollais A., Meda P., Allagnat F.
ISSN
1479-6813 (Electronic)
ISSN-L
0952-5041
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
51
Numéro
1
Pages
49-58
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: epublish
Résumé
Channels formed by the gap junction protein Connexin36 (CX36) contribute to the proper control of insulin secretion. We previously demonstrated that chronic exposure to glucose decreases Cx36 levels in insulin-secreting cells in vitro. Here, we investigated whether hyperglycemia also regulates Cx36 in vivo. Using a model of continuous glucose infusion in adult rats, we showed that prolonged (24-48 h) hyperglycemia reduced the Cx36 gene Gjd2 mRNA levels in pancreatic islets. Accordingly, prolonged exposure to high glucose concentrations also reduced the expression and function of Cx36 in the rat insulin-producing INS-1E cell line. The glucose effect was blocked after inhibition of the cAMP/PKA pathway and was associated with an overexpression of the inducible cAMP early repressor ICER-1/ICER-1γ, which binds to a functional cAMP-response element in the promoter of the Cx36 gene Gjd2. The involvement of this repressor was further demonstrated using an antisense strategy of ICER-1 inhibition, which prevented glucose-induced downregulation of Cx36. The data indicate that chronic exposure to glucose alters the in vivo expression of Cx36 by the insulin-producing β-cells through ICER-1/ICER-1γ overexpression. This mechanism may contribute to the reduced glucose sensitivity and altered insulin secretion, which contribute to the pathophysiology of diabetes.
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/09/2013 10:18
Dernière modification de la notice
20/08/2019 14:34
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