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Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia in the male mice

Author

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  • Ling Liu

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center
    University of Science and Technology of China)

  • Zhaohuan Huang

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center)

  • Jian Zhang

    (University of Science and Technology of China)

  • Mengtian Wang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Ting Yue

    (University of Science and Technology of China)

  • Wei Wang

    (University of Science and Technology of China)

  • Yue Wu

    (University of Science and Technology of China)

  • Zhi Zhang

    (University of Science and Technology of China
    University of Science and Technology of China)

  • Wei Xiong

    (Hefei Comprehensive National Science Center
    University of Science and Technology of China)

  • Chao Wang

    (University of Science and Technology of China)

  • Feng Wu

    (Hefei Comprehensive National Science Center
    University of Science and Technology of China)

  • Cheng Zhan

    (University of Science and Technology of China)

  • Guoqiang Bi

    (Hefei Comprehensive National Science Center
    University of Science and Technology of China)

  • Ji Liu

    (University of Science and Technology of China
    Hefei Comprehensive National Science Center
    University of Science and Technology of China
    University of Science and Technology of China)

Abstract

Rapid glucose supply is crucial for animal survival during stress response. How the timescale of stress-induced glucose release precisely controlled by hypothalamic corticotropin-releasing hormone (CRH) neurons remains unclear. Here, we show that stress-induced hyperglycemia can be divided into at least two stages in male mice: the first fast stage is mediated by hypothalamus (paraventricular to ventromedial hypothalamus)-sympathetic (raphe pallidus nucleus to intermediolateral nucleus)-liver (HSL) axis activity; the second delayed stage is mediated by adrenal activity. Blocking the activity of HSL axis impairs predatory evoked flight responses, indicating that the HSL pathway activity is necessary for stress coping. We further reveal the intracellular signal cascade for CRH signal in the hypothalamus, which is mediated by GABAA receptor β3 subunit phosphorylation at S408/409, results in prevention of GABAA receptor membrane recruitment. Thus, we uncovered the precise timescale of glucose supply during stress which is mediated by adrenal independent HSL and adrenal dependent pathway respectively.

Suggested Citation

  • Ling Liu & Zhaohuan Huang & Jian Zhang & Mengtian Wang & Ting Yue & Wei Wang & Yue Wu & Zhi Zhang & Wei Xiong & Chao Wang & Feng Wu & Cheng Zhan & Guoqiang Bi & Ji Liu, 2024. "Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia in the male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52815-3
    DOI: 10.1038/s41467-024-52815-3
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    References listed on IDEAS

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    1. Yanlin He & Pingwen Xu & Chunmei Wang & Yan Xia & Meng Yu & Yongjie Yang & Kaifan Yu & Xing Cai & Na Qu & Kenji Saito & Julia Wang & Ilirjana Hyseni & Matthew Robertson & Badrajee Piyarathna & Min Gao, 2020. "Estrogen receptor-α expressing neurons in the ventrolateral VMH regulate glucose balance," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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