liveonearth (liveonearth) wrote,
liveonearth
liveonearth

Steroid and Vitamin D Receptors implicated in Epigenetics of Insulin Resistance

EPIGENETICS OF DM2: GLUCOCORTICOID AND VIT D RECEPTORS MEDIATE
ALSO TNF ALPHA OR DEXAMETHASONE INDUCES IR
http://www.nature.com/ncb/journal/v17/n1/full/ncb3080.html
Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis
Sona Kang, Linus T. Tsai, Yiming Zhou, Adam Evertts, Su Xu, Michael J. Griffin, Robbyn Issner, Holly J. Whitton, Benjamin A. Garcia, Charles B. Epstein, Tarjei S. Mikkelsen & Evan D. Rosen
Nature Cell Biology 17, 44–56 (2015) doi:10.1038/ncb3080
Received 06 August 2014 Accepted Nov 2014 Published online 15 Dec 2014
Abstract
Insulin resistance is a cardinal feature of Type 2 diabetes (T2D) and a frequent complication of multiple clinical conditions, including obesity, ageing and steroid use, among others. How such a panoply of insults can result in a common phenotype is incompletely understood. Furthermore, very little is known about the transcriptional and epigenetic basis of this disorder, despite evidence that such pathways are likely to play a fundamental role. Here, we compare cell autonomous models of insulin resistance induced by the cytokine tumour necrosis factor-α or by the steroid dexamethasone to construct detailed transcriptional and epigenomic maps associated with cellular insulin resistance. These data predict that the glucocorticoid receptor and vitamin D receptor are common mediators of insulin resistance, which we validate using gain- and loss-of-function studies. These studies define a common transcriptional and epigenomic signature in cellular insulin resistance enabling the identification of pathogenic mechanisms.
Tags: diabetes, epigenetics, immunology, insulin, obesity, steroids, vit d
Subscribe
  • Post a new comment

    Error

    Comments allowed for friends only

    Anonymous comments are disabled in this journal

    default userpic

    Your reply will be screened

    Your IP address will be recorded 

  • 0 comments