Journal article
Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
Nature communications, Vol.14(1), 3143
05/30/2023
DOI: 10.1038/s41467-023-38584-5
PMCID: PMC10229547
PMID: 37253782
Abstract
The classical dogma of glucocorticoid-induced insulin resistance is that it is caused by the transcriptional activation of hepatic gluconeogenic and insulin resistance genes by the glucocorticoid receptor (GR). Here, we find that glucocorticoids also stimulate the expression of insulin-sensitizing genes, such as
Irs2
. The transcriptional coregulator EHMT2 can serve as a transcriptional coactivator or a corepressor. Using male mice that have a defective EHMT2 coactivation function specifically, we show that glucocorticoid-induced
Irs2
transcription is dependent on liver EHMT2’s coactivation function and that IRS2 play a key role in mediating the limitation of glucocorticoid-induced insulin resistance by EHMT2’s coactivation. Overall, we propose a model in which glucocorticoid-regulated insulin sensitivity is determined by the balance between glucocorticoid-modulated insulin resistance and insulin sensitizing genes, in which EHMT2 coactivation is specifically involved in the latter process.
Glucocorticoids are known to induce insulin resistance via transcriptional activation of genes related to liver gluconeogenesis and insulin resistance. Here the authors report that in male mice treated with glucocorticoids, the transcriptional co-regulator EHMT2 is involved in the induction of
Irs2
(a gene promoting insulin action) to restrict the extent of insulin resistance in the liver.
Details
- Title: Subtitle
- Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
- Creators
- Rebecca A. Lee - University of California, BerkeleyMaggie Chang - University of California, BerkeleyNicholas Yiv - University of California, BerkeleyAriel Tsay - University of California, BerkeleySharon Tian - University of California, BerkeleyDanielle Li - University of California, BerkeleyCoralie Poulard - InsermMichael R. Stallcup - University of Southern CaliforniaMiles A. Pufall - University of IowaJen-Chywan Wang - University of California, Berkeley
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.14(1), 3143
- DOI
- 10.1038/s41467-023-38584-5
- PMID
- 37253782
- PMCID
- PMC10229547
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Publisher
- Nature Publishing Group UK
- Grant note
- R01 DK124866 / ;
- Language
- English
- Date published
- 05/30/2023
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984421707102771
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