Wan L, Gao Q, Deng Y, Ke Y, Ma E, Yang H, Lin H, Li H, Yang Y, Gong J, Li J, Xu Y, Liu J, Li J, Liu J, Zhang X, Huang L, Feng J, Zhang Y, Huang H, Wang H, Wang C, Chen Q, Huang X, Ye Q, Li D, Yan Q, Liu M, Wei M, Mo Y, Li D, Tang K, Lin C, Zheng F, Xu L, Cheng G, Wang P, Yang X, Wu F, Sun Z, Qin C, Wei C, Zhong H

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. ...

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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.

Date: Jan. 01, 2022

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