2. Academic Validation
  3. Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia in the male mice

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

  • Nat Commun. 2024 Oct 5;15(1):8632. doi: 10.1038/s41467-024-52815-3.
Ling Liu # 1 2 3,  Zhaohuan Huang # 1 2,  Jian Zhang # 3,  Mengtian Wang 1 4,  Ting Yue 3,  Wei Wang 1,  Yue Wu 1,  Zhi Zhang 3 5,  Wei Xiong 2 6,  Chao Wang 6,  Feng Wu 2 4,  Cheng Zhan 7,  Guoqiang Bi 2 3,  Ji Liu 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Endocrinology, The First Affiliated Hospital of USTC, National Engineering Laboratory for Brain-inspired Intelligence Technology and Application, School of Information Science and Technology, University of Science and Technology of China, Huangshan Road 443, Hefei, 230027, China.
  • 2 Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, West WangJiang Road 5089, Hefei, 230088, China.
  • 3 CAS Key Laboratory of Brain Function and Diseases, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Huangshan Road 443, Hefei, 230027, China.
  • 4 MoE Key Laboratory of Brain-inspired Intelligent Perception and Cognition, University of Science and Technology of China, Huangshan Road 443, Hefei, 230027, China.
  • 5 Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, LuJiang Road 17, Hefei, 230001, China.
  • 6 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, LuJiang Road 17, Hefei, 230001, China.
  • 7 Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, LuJiang Road 17, Hefei, 230001, China.
  • 8 Department of Endocrinology, The First Affiliated Hospital of USTC, National Engineering Laboratory for Brain-inspired Intelligence Technology and Application, School of Information Science and Technology, University of Science and Technology of China, Huangshan Road 443, Hefei, 230027, China. Lj1257@ustc.edu.cn.
  • 9 Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, West WangJiang Road 5089, Hefei, 230088, China. Lj1257@ustc.edu.cn.
  • 10 CAS Key Laboratory of Brain Function and Diseases, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Huangshan Road 443, Hefei, 230027, China. Lj1257@ustc.edu.cn.
  • 11 MoE Key Laboratory of Brain-inspired Intelligent Perception and Cognition, University of Science and Technology of China, Huangshan Road 443, Hefei, 230027, China. Lj1257@ustc.edu.cn.
  • # Contributed equally.
PMID: 39366937 DOI: 10.1038/s41467-024-52815-3
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.

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