tetano
Editor, Senior Moderator
Nat Metab
. 2022 Jan 6.
doi: 10.1038/s42255-021-00508-2. Online ahead of print.
GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia
Luming Wan[SUP] #[/SUP][SUP] 1 [/SUP], Qi Gao[SUP] #[/SUP][SUP] 2 [/SUP], Yongqiang Deng[SUP] #[/SUP][SUP] 3 [/SUP], Yuehua Ke[SUP] #[/SUP][SUP] 4 [/SUP], Enhao Ma[SUP] #[/SUP][SUP] 5 [/SUP], Huan Yang[SUP] #[/SUP][SUP] 1 6 [/SUP], Haotian Lin[SUP] #[/SUP][SUP] 1 [/SUP], Huilong Li[SUP] 1 6 [/SUP], Yilong Yang[SUP] 1 [/SUP], Jing Gong[SUP] 1 [/SUP], Jingfei Li[SUP] 1 [/SUP], Yixin Xu[SUP] 1 [/SUP], Jing Liu[SUP] 1 [/SUP], Jianmin Li[SUP] 1 [/SUP], Jialong Liu[SUP] 1 [/SUP], Xuemiao Zhang[SUP] 1 [/SUP], Linfei Huang[SUP] 1 [/SUP], Jiangyue Feng[SUP] 1 [/SUP], Yanhong Zhang[SUP] 1 [/SUP], Hanqing Huang[SUP] 1 [/SUP], Huapeng Wang[SUP] 1 [/SUP], Changjun Wang[SUP] 4 [/SUP], Qi Chen[SUP] 3 [/SUP], Xingyao Huang[SUP] 3 [/SUP], Qing Ye[SUP] 3 [/SUP], Dongyu Li[SUP] 1 [/SUP], Qiulin Yan[SUP] 1 [/SUP], Muyi Liu[SUP] 1 [/SUP], Meng Wei[SUP] 1 [/SUP], Yunhai Mo[SUP] 1 [/SUP], Dongrui Li[SUP] 1 [/SUP], Ke Tang[SUP] 1 [/SUP], Changqing Lin[SUP] 2 [/SUP], Fei Zheng[SUP] 2 [/SUP], Lei Xu[SUP] 2 [/SUP], Gong Cheng[SUP] 5 [/SUP], Peihui Wang[SUP] 7 [/SUP], Xiaopan Yang[SUP] 1 [/SUP], Feixang Wu[SUP] 6 [/SUP], Zhiwei Sun[SUP] 2 [/SUP], Chengfeng Qin[SUP] 3 [/SUP], Congwen Wei[SUP] 1 [/SUP], Hui Zhong[SUP] 8 [/SUP]
Affiliations
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.
. 2022 Jan 6.
doi: 10.1038/s42255-021-00508-2. Online ahead of print.
GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia
Luming Wan[SUP] #[/SUP][SUP] 1 [/SUP], Qi Gao[SUP] #[/SUP][SUP] 2 [/SUP], Yongqiang Deng[SUP] #[/SUP][SUP] 3 [/SUP], Yuehua Ke[SUP] #[/SUP][SUP] 4 [/SUP], Enhao Ma[SUP] #[/SUP][SUP] 5 [/SUP], Huan Yang[SUP] #[/SUP][SUP] 1 6 [/SUP], Haotian Lin[SUP] #[/SUP][SUP] 1 [/SUP], Huilong Li[SUP] 1 6 [/SUP], Yilong Yang[SUP] 1 [/SUP], Jing Gong[SUP] 1 [/SUP], Jingfei Li[SUP] 1 [/SUP], Yixin Xu[SUP] 1 [/SUP], Jing Liu[SUP] 1 [/SUP], Jianmin Li[SUP] 1 [/SUP], Jialong Liu[SUP] 1 [/SUP], Xuemiao Zhang[SUP] 1 [/SUP], Linfei Huang[SUP] 1 [/SUP], Jiangyue Feng[SUP] 1 [/SUP], Yanhong Zhang[SUP] 1 [/SUP], Hanqing Huang[SUP] 1 [/SUP], Huapeng Wang[SUP] 1 [/SUP], Changjun Wang[SUP] 4 [/SUP], Qi Chen[SUP] 3 [/SUP], Xingyao Huang[SUP] 3 [/SUP], Qing Ye[SUP] 3 [/SUP], Dongyu Li[SUP] 1 [/SUP], Qiulin Yan[SUP] 1 [/SUP], Muyi Liu[SUP] 1 [/SUP], Meng Wei[SUP] 1 [/SUP], Yunhai Mo[SUP] 1 [/SUP], Dongrui Li[SUP] 1 [/SUP], Ke Tang[SUP] 1 [/SUP], Changqing Lin[SUP] 2 [/SUP], Fei Zheng[SUP] 2 [/SUP], Lei Xu[SUP] 2 [/SUP], Gong Cheng[SUP] 5 [/SUP], Peihui Wang[SUP] 7 [/SUP], Xiaopan Yang[SUP] 1 [/SUP], Feixang Wu[SUP] 6 [/SUP], Zhiwei Sun[SUP] 2 [/SUP], Chengfeng Qin[SUP] 3 [/SUP], Congwen Wei[SUP] 1 [/SUP], Hui Zhong[SUP] 8 [/SUP]
Affiliations
- 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.