SARS-CoV-2 infects human pancreatic ß cells and elicits ß cell impairment.
Cell Metab
; 33(8): 1565-1576.e5, 2021 08 03.
Article
in English
| MEDLINE | ID: covidwho-1343160
ABSTRACT
Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic ß cells can be infected by SARS-CoV-2 and cause ß cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in ß cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic ß cells in patients who succumbed to COVID-19 and selectively infects human islet ß cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces ß cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic ß cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce ß cell killing.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Receptors, Virus
/
Neuropilin-1
/
Diabetes Mellitus
/
Insulin-Secreting Cells
/
Virus Internalization
/
SARS-CoV-2
/
COVID-19
Type of study:
Diagnostic study
/
Observational study
/
Prognostic study
Topics:
Long Covid
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
Cell Metab
Journal subject:
Metabolism
Year:
2021
Document Type:
Article
Affiliation country:
J.cmet.2021.05.013
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