Evidence against a direct role of klotho in insulin resistance.

Détails

ID Serval
serval:BIB_0AA9B4D1F08B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Evidence against a direct role of klotho in insulin resistance.
Périodique
Pflügers Archiv : European Journal of Physiology
Auteur(s)
Lorenzi Olivier, Veyrat-Durebex Christelle, Wollheim Claes B., Villemin Pascal, Rohner-Jeanrenaud Francoise, Zanchi Anne, Vischer Ulrich M.
ISSN
1432-2013[electronic]
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
459
Numéro
3
Pages
465-473
Langue
anglais
Résumé
The klotho gene may be involved in the aging process. Klotho is a coactivator of FGF23, a regulator of phosphate and vitamin D metabolism. It has also been reported to be downregulated in insulin resistance syndromes and paradoxically to directly inhibit IGF-1 and insulin signaling. Our aim was to study klotho's regulation and effects on insulin and IGF-1 signaling to unravel this paradox. We studied klotho tissue distribution and expression by quantitative real-time polymerase chain reaction and Western blotting in obese Zucker rats and high-fat fed Wistar rats, two models of insulin resistance. Klotho was expressed in kidneys but at much lower levels (<1.5%) in liver, muscle, brain, and adipose tissue. There were no significant differences between insulin resistant and control animals. We next produced human recombinant soluble klotho protein (KLEC) and studied its effects on insulin and IGF-1 signaling in cultured cells. In HEK293 cells, FGF23 signaling (judged by FRS2-alpha and ERK1/2 phosphorylation) was activated by conditioned media from KLEC-producing cells (CM-KLEC); however, IGF-1 signaling was unaffected. CM-KLEC did not inhibit IGF-1 and insulin signaling in L6 and Hep G2 cells, as judged by Akt and ERK1/2 phosphorylation. We conclude that decreased klotho expression is not a general feature of rodent models of insulin resistance. Further, the soluble klotho protein does not inhibit IGF-1 and/or insulin signaling in HEK293, L6, and HepG2 cells, arguing against a direct role of klotho in insulin signaling. However, the hypothesis that klotho indirectly regulates insulin sensitivity via FGF23 activation remains to be investigated.
Mots-clé
Klotho, Aging, Insulin Resistance, FGF23, Primary Hyperparathyroidism, Endothelial Dysfunction, Glucose-Tolerance, Oxidative Stress, Hormone Klotho, Mice, Phosphate, Cleavage, Receptor, Gene
Pubmed
Web of science
Création de la notice
14/10/2009 11:16
Dernière modification de la notice
03/03/2018 13:34
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