CDK4 is an essential insulin effector in adipocytes.

Details

Serval ID
serval:BIB_E56CC40E7CB9
Type
Article: article from journal or magazin.
Collection
Publications
Title
CDK4 is an essential insulin effector in adipocytes.
Journal
Journal of Clinical Investigation
Author(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
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
126
Number
1
Pages
335-348
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
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
Create date
02/02/2016 18:23
Last modification date
20/08/2019 17:08
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