Sodium/hydrogen exchanger NHA2 is critical for insulin secretion in β-cells.

Détails

ID Serval
serval:BIB_D523B7B158A1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Sodium/hydrogen exchanger NHA2 is critical for insulin secretion in β-cells.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Deisl C., Simonin A., Anderegg M., Albano G., Kovacs G., Ackermann D., Moch H., Dolci W., Thorens B., A Hediger M., Fuster D.G.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
110
Numéro
24
Pages
10004-10009
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
NHA2 is a sodium/hydrogen exchanger with unknown physiological function. Here we show that NHA2 is present in rodent and human β-cells, as well as β-cell lines. In vivo, two different strains of NHA2-deficient mice displayed a pathological glucose tolerance with impaired insulin secretion but normal peripheral insulin sensitivity. In vitro, islets of NHA2-deficient and heterozygous mice, NHA2-depleted Min6 cells, or islets treated with an NHA2 inhibitor exhibited reduced sulfonylurea- and secretagogue-induced insulin secretion. The secretory deficit could be rescued by overexpression of a wild-type, but not a functionally dead, NHA2 transporter. NHA2 deficiency did not affect insulin synthesis or maturation and had no impact on basal or glucose-induced intracellular Ca(2+) homeostasis in islets. Subcellular fractionation and imaging studies demonstrated that NHA2 resides in transferrin-positive endosomes and synaptic-like microvesicles but not in insulin-containing large dense core vesicles in β-cells. Loss of NHA2 inhibited clathrin-dependent, but not clathrin-independent, endocytosis in Min6 and primary β-cells, suggesting defective endo-exocytosis coupling as the underlying mechanism for the secretory deficit. Collectively, our in vitro and in vivo studies reveal the sodium/proton exchanger NHA2 as a critical player for insulin secretion in the β-cell. In addition, our study sheds light on the biological function of a member of this recently cloned family of transporters.
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/08/2013 8:47
Dernière modification de la notice
20/08/2019 15:54
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