GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia

  • Nat Metab. 2022 Jan;4(1):29-43. doi: 10.1038/s42255-021-00508-2.
Luming Wan   #  1 ,  Qi Gao   #  2 ,  Yongqiang Deng   #  3 ,  Yuehua Ke   #  4 ,  Enhao Ma   #  5 ,  Huan Yang   #  1  6 ,  Haotian Lin   #  1 ,  Huilong Li  1  6 ,  Yilong Yang  1 ,  Jing Gong  1 ,  Jingfei Li  1 ,  Yixin Xu  1 ,  Jing Liu  1 ,  Jianmin Li  1 ,  Jialong Liu  1 ,  Xuemiao Zhang  1 ,  Linfei Huang  1 ,  Jiangyue Feng  1 ,  Yanhong Zhang  1 ,  Hanqing Huang  1 ,  Huapeng Wang  1 ,  Changjun Wang  4 ,  Qi Chen  3 ,  Xingyao Huang  3 ,  Qing Ye  3 ,  Dongyu Li  1 ,  Qiulin Yan  1 ,  Muyi Liu  1 ,  Meng Wei  1 ,  Yunhai Mo  1 ,  Dongrui Li  1 ,  Ke Tang  1 ,  Changqing Lin  2 ,  Fei Zheng  2 ,  Lei Xu  2 ,  Gong Cheng  5 ,  Peihui Wang  7 ,  Xiaopan Yang  1 ,  Feixang Wu  6 ,  Zhiwei Sun  2 ,  Chengfeng Qin  3 ,  Congwen Wei  1 ,  Hui Zhong  8
Affiliations
  • 1. Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China.
  • 2. Beijing Sungen Biomedical Technology Co. Ltd., Beijing, China.
  • 3. Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, China.
  • 4. Centers for Disease Control and Prevention of PLA, Beijing, China.
  • 5. Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing, China.
  • 6. Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China.
  • 7. Key Laboratory for Experimental Teratology of Ministry of Education and Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 8. Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing, China. [email protected].
  • # Contributed equally.
PMID: 34992299 DOI: 10.1038/s42255-021-00508-2
Abstract

Severe cases of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 Infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 Infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in Lungs and Livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic Glucose Metabolism.

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