GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia.
Nat Metab
; 4(1): 29-43, 2022 01.
Article
in English
| MEDLINE | ID: covidwho-1612214
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
SARS-CoV-2
/
COVID-19
/
Glucose
/
Hyperglycemia
/
Membrane Proteins
Type of study:
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Animals
/
Humans
Language:
English
Journal:
Nat Metab
Year:
2022
Document Type:
Article
Affiliation country:
S42255-021-00508-2
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