CDK4 is an essential insulin effector in adipocytes.

Détails

ID Serval
serval:BIB_E56CC40E7CB9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
CDK4 is an essential insulin effector in adipocytes.
Périodique
Journal of Clinical Investigation
Auteur(s)
Lagarrigue S., Lopez-Mejia I.C., Denechaud P.D., Escoté X., Castillo-Armengol J., Jimenez V., Chavey C., Giralt A., Lai Q., Zhang L., Martinez-Carreres L., Delacuisine B., Annicotte J.S., Blanchet E., Huré S., Abella A., Tinahones F.J., Vendrell J., Dubus P., Bosch F., Kahn C.R., Fajas L.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
126
Numéro
1
Pages
335-348
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.
Pubmed
Web of science
Création de la notice
02/02/2016 17:23
Dernière modification de la notice
20/08/2019 16:08
Données d'usage