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Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice

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 g...

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Autores principales: Lee, Rebecca A., Chang, Maggie, Yiv, Nicholas, Tsay, Ariel, Tian, Sharon, Li, Danielle, Poulard, Coralie, Stallcup, Michael R., Pufall, Miles A., Wang, Jen-Chywan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229547/
https://www.ncbi.nlm.nih.gov/pubmed/37253782
http://dx.doi.org/10.1038/s41467-023-38584-5
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author Lee, Rebecca A.
Chang, Maggie
Yiv, Nicholas
Tsay, Ariel
Tian, Sharon
Li, Danielle
Poulard, Coralie
Stallcup, Michael R.
Pufall, Miles A.
Wang, Jen-Chywan
author_facet Lee, Rebecca A.
Chang, Maggie
Yiv, Nicholas
Tsay, Ariel
Tian, Sharon
Li, Danielle
Poulard, Coralie
Stallcup, Michael R.
Pufall, Miles A.
Wang, Jen-Chywan
author_sort Lee, Rebecca A.
collection PubMed
description 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.
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spelling pubmed-102295472023-06-01 Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice Lee, Rebecca A. Chang, Maggie Yiv, Nicholas Tsay, Ariel Tian, Sharon Li, Danielle Poulard, Coralie Stallcup, Michael R. Pufall, Miles A. Wang, Jen-Chywan Nat Commun Article 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. Nature Publishing Group UK 2023-05-30 /pmc/articles/PMC10229547/ /pubmed/37253782 http://dx.doi.org/10.1038/s41467-023-38584-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lee, Rebecca A.
Chang, Maggie
Yiv, Nicholas
Tsay, Ariel
Tian, Sharon
Li, Danielle
Poulard, Coralie
Stallcup, Michael R.
Pufall, Miles A.
Wang, Jen-Chywan
Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
title Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
title_full Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
title_fullStr Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
title_full_unstemmed Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
title_short Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice
title_sort transcriptional coactivation by ehmt2 restricts glucocorticoid-induced insulin resistance in a study with male mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229547/
https://www.ncbi.nlm.nih.gov/pubmed/37253782
http://dx.doi.org/10.1038/s41467-023-38584-5
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