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

Author

Listed:
  • Rebecca A. Lee

    (University of California Berkeley
    University of California Berkeley)

  • Maggie Chang

    (University of California Berkeley
    University of California Berkeley)

  • Nicholas Yiv

    (University of California Berkeley
    University of California Berkeley)

  • Ariel Tsay

    (University of California Berkeley
    University of California Berkeley)

  • Sharon Tian

    (University of California Berkeley)

  • Danielle Li

    (University of California Berkeley)

  • Coralie Poulard

    (Inserm U1052, Centre de Recherche en Cancérologie de Lyon)

  • Michael R. Stallcup

    (University of Southern California)

  • Miles A. Pufall

    (University of Iowa Carver College of Medicine)

  • Jen-Chywan Wang

    (University of California Berkeley
    University of California Berkeley
    University of California Berkeley)

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.

Suggested Citation

  • Rebecca A. Lee & Maggie Chang & Nicholas Yiv & Ariel Tsay & Sharon Tian & Danielle Li & Coralie Poulard & Michael R. Stallcup & Miles A. Pufall & Jen-Chywan Wang, 2023. "Transcriptional coactivation by EHMT2 restricts glucocorticoid-induced insulin resistance in a study with male mice," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38584-5
    DOI: 10.1038/s41467-023-38584-5
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    References listed on IDEAS

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    1. Sílvia Bonàs-Guarch & Marta Guindo-Martínez & Irene Miguel-Escalada & Niels Grarup & David Sebastian & Elias Rodriguez-Fos & Friman Sánchez & Mercè Planas-Fèlix & Paula Cortes-Sánchez & Santi González, 2018. "Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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