1. Academic Validation
  2. GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia

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

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.
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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