| First Author | Wan L | Year | 2022 |
| Journal | Nat Metab | Volume | 4 |
| Issue | 1 | Pages | 29-43 |
| PubMed ID | 34992299 | Mgi Jnum | J:335014 |
| Mgi Id | MGI:7443297 | Doi | 10.1038/s42255-021-00508-2 |
| Citation | Wan L, et al. (2022) GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia. Nat Metab 4(1):29-43 |
| abstractText | 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. |
