tetano
Editor, Senior Moderator
Cell Metab
. 2021 May 18;S1550-4131(21)00230-8.
doi: 10.1016/j.cmet.2021.05.013. Online ahead of print.
SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment
Chien-Ting Wu[SUP] 1 [/SUP], Peter V Lidsky[SUP] 2 [/SUP], Yinghong Xiao[SUP] 2 [/SUP], Ivan T Lee[SUP] 3 [/SUP], Ran Cheng[SUP] 4 [/SUP], Tsuguhisa Nakayama[SUP] 5 [/SUP], Sizun Jiang[SUP] 6 [/SUP], Janos Demeter[SUP] 1 [/SUP], Romina J Bevacqua[SUP] 7 [/SUP], Charles A Chang[SUP] 8 [/SUP], Robert L Whitener[SUP] 7 [/SUP], Anna K Stalder[SUP] 9 [/SUP], Bokai Zhu[SUP] 6 [/SUP], Han Chen[SUP] 6 [/SUP], Yury Goltsev[SUP] 6 [/SUP], Alexandar Tzankov[SUP] 9 [/SUP], Jayakar V Nayak[SUP] 10 [/SUP], Garry P Nolan[SUP] 6 [/SUP], Matthias S Matter[SUP] 11 [/SUP], Raul Andino[SUP] 12 [/SUP], Peter K Jackson[SUP] 13 [/SUP]
Affiliations
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 β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.
Keywords: ACE2; COVID-19; SARS-CoV-2; SARS-CoV-2 spike protein; apoptosis; insulin; neuropilin 1; pancreatic beta cell; phosphoproteomics; type 1 diabetes.
. 2021 May 18;S1550-4131(21)00230-8.
doi: 10.1016/j.cmet.2021.05.013. Online ahead of print.
SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment
Chien-Ting Wu[SUP] 1 [/SUP], Peter V Lidsky[SUP] 2 [/SUP], Yinghong Xiao[SUP] 2 [/SUP], Ivan T Lee[SUP] 3 [/SUP], Ran Cheng[SUP] 4 [/SUP], Tsuguhisa Nakayama[SUP] 5 [/SUP], Sizun Jiang[SUP] 6 [/SUP], Janos Demeter[SUP] 1 [/SUP], Romina J Bevacqua[SUP] 7 [/SUP], Charles A Chang[SUP] 8 [/SUP], Robert L Whitener[SUP] 7 [/SUP], Anna K Stalder[SUP] 9 [/SUP], Bokai Zhu[SUP] 6 [/SUP], Han Chen[SUP] 6 [/SUP], Yury Goltsev[SUP] 6 [/SUP], Alexandar Tzankov[SUP] 9 [/SUP], Jayakar V Nayak[SUP] 10 [/SUP], Garry P Nolan[SUP] 6 [/SUP], Matthias S Matter[SUP] 11 [/SUP], Raul Andino[SUP] 12 [/SUP], Peter K Jackson[SUP] 13 [/SUP]
Affiliations
- PMID: 34081912
- PMCID: PMC8130512
- DOI: 10.1016/j.cmet.2021.05.013
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 β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing.
Keywords: ACE2; COVID-19; SARS-CoV-2; SARS-CoV-2 spike protein; apoptosis; insulin; neuropilin 1; pancreatic beta cell; phosphoproteomics; type 1 diabetes.