SARS-CoV-2 infects human pancreatic ß cells and elicits ß cell impairment.
Cell Metab
; 33(8): 1565-1576.e5, 2021 08 03.
Artículo
en Inglés
| 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.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Receptores Virales
/
Neuropilina-1
/
Diabetes Mellitus
/
Células Secretoras de Insulina
/
Internalización del Virus
/
SARS-CoV-2
/
COVID-19
Tipo de estudio:
Estudios diagnósticos
/
Estudio observacional
/
Estudio pronóstico
Tópicos:
Covid persistente
Límite:
Adulto
/
Anciano
/
Femenino
/
Humanos
/
Masculino
/
Middle aged
Idioma:
Inglés
Revista:
Cell Metab
Asunto de la revista:
Metabolismo
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
J.cmet.2021.05.013
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