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  3. Glucose-sensing glucagon-like peptide-1 receptor neurons in the dorsomedial hypothalamus regulate glucose metabolism

Glucose-sensing glucagon-like peptide-1 receptor neurons in the dorsomedial hypothalamus regulate glucose metabolism

  • Sci Adv. 2022 Jun 10;8(23):eabn5345. doi: 10.1126/sciadv.abn5345.
Zhaohuan Huang 1 2,  Ling Liu 1 2,  Jian Zhang 3,  Kristie Conde 4 5,  Jay Phansalkar 4 5,  Zhongzhong Li 1,  Lei Yao 3,  Zihui Xu 4 5,  Wei Wang 6,  Jiangning Zhou 3,  Guoqiang Bi 2 3,  Feng Wu 1 2,  Randy J Seeley 7,  Michael M Scott 8,  Cheng Zhan 9 10 11,  Zhiping P Pang 4 5,  Ji Liu 1 2 3
Affiliations

Affiliations

  • 1 National Engineering Laboratory for Brain-inspired Intelligence Technology and Application, School of Information Science and Technology, University of Science and Technology of China, Anhui, China.
  • 2 Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China.
  • 3 CAS Key Laboratory of Brain Function and Diseases, Life Science School, University of Science and Technology of China, Anhui, China.
  • 4 Child Health Institute of New Jersey, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
  • 5 Department of Neuroscience and Cell Biology, Rutgers University Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
  • 6 Department of Endocrinology and Laboratory for Diabetes, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui, China.
  • 7 Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
  • 8 Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
  • 9 Department of Hematology, The First Affiliated Hospital, Life Science School, University of Science and Technology of China, Anhui, China.
  • 10 National Institute of Biological Sciences, Beijing 102206, China.
  • 11 Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 100084, China.
PMID: 35675406 DOI: 10.1126/sciadv.abn5345
Abstract

Glucagon-like peptide-1 (GLP-1) regulates energy homeostasis via activation of the GLP-1 receptors (GLP-1Rs) in the central nervous system. However, the mechanism by which the central GLP-1 signal controls blood glucose levels, especially in different nutrient states, remains unclear. Here, we defined a population of glucose-sensing GLP-1R neurons in the dorsomedial hypothalamic nucleus (DMH), by which endogenous GLP-1 decreases glucose levels via the cross-talk between the hypothalamus and pancreas. Specifically, we illustrated the sufficiency and necessity of DMHGLP-1R in glucose regulation. The activation of the DMHGLP-1R neurons is mediated by a cAMP-PKA-dependent inhibition of a delayed rectifier potassium current. We also dissected a descending control of DMHGLP-1R -dorsal motor nucleus of the vagus nerve (DMV)-pancreas activity that can regulate glucose levels by increasing Insulin release. Thus, our results illustrate how central GLP-1 action in the DMH can induce a nutrient state-dependent reduction in blood glucose level.

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