SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment.

Cell Metabolism
Chien-Ting WuPeter K Jackson

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.

References

Apr 13, 2004·Oncogene·Teiji Wada, Josef M Penninger
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 6, 2007·Nucleic Acids Research·Rune LindingTony Pawson
Oct 22, 2008·Oncogene·D N Dhanasekaran, E P Reddy
Dec 21, 2011·The Journal of Clinical Investigation·Andrew F ZiolkowskiCharmaine J Simeonovic
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Justin M DrakeOwen N Witte
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Dec 18, 2014·Nucleic Acids Research·Peter V HornbeckElzbieta Skrzypek
Nov 27, 2015·Life Sciences·Bin GuoXiuli Men
Sep 27, 2016·Cell Metabolism·Åsa SegerstolpeRickard Sandberg
Dec 3, 2016·Molecular Systems Biology·David OchoaPedro Beltrao
Feb 16, 2017·Bioinformatics·Claudia Hernandez-ArmentaPedro Beltrao
Nov 6, 2018·Molecular & Cellular Proteomics : MCP·Florian MeierMatthias Mann
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Mar 3, 2020·Frontiers in Cell and Developmental Biology·Vanessa HabergerEberhard Hildt
Mar 7, 2020·Nature Reviews. Cardiology·Ying-Ying ZhengXiang Xie
Mar 15, 2020·The Lancet. Respiratory Medicine·Lei FangMichael Roth
Mar 28, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Andrea GiacomelliMassimo Galli
Apr 28, 2020·Diabetes Research and Clinical Practice·Ying Jie CheeEster Yeoh
May 3, 2020·Science·Mart M LamersHans Clevers
May 14, 2020·The New England Journal of Medicine·Victor G PuellesTobias B Huber
Jun 13, 2020·The New England Journal of Medicine·Francesco RubinoEric Renard
Aug 28, 2020·Diabetes Research and Clinical Practice·Awadhesh Kumar Singh, Ritu Singh
Sep 25, 2020·Cell·Thomas Mandel ClausenJeffrey D Esko
Oct 22, 2020·Science·Ludovico Cantuti-CastelvetriMikael Simons
Oct 22, 2020·Science·James L DalyYohei Yamauchi
Oct 30, 2020·Nature Communications·Ivan T LeePeter K Jackson
Nov 13, 2020·Journal of Pediatric Endocrinology & Metabolism : JPEM·Monica N NaguibAlaina P Vidmar
Jan 6, 2021·Diabetes & Metabolic Syndrome·Sirisha Kusuma BodduMohammad Shafi Kuchay
Feb 5, 2021·Nature Metabolism·Janis A MüllerAlexander Kleger

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Citations

Jul 17, 2021·Journal of the Pediatric Infectious Diseases Society·Ravi JhaveriTheoklis Zaoutis
Aug 11, 2021·Trends in Endocrinology and Metabolism : TEM·Shirin GeravandiAmin Ardestani
Aug 28, 2021·Cells·Maximilian HirschenbergerKonstantin Maria Johannes Sparrer
Aug 27, 2021·Journal of Fungi·Hariprasath PrakashShivaprakash Mandya Rudramurthy
Aug 24, 2021·Cell Reports Medicine·Amy L Clark, Raghavendra G Mirmira

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Software Mentioned

FIJI
PhosphositePlus
timsTOF
ksea
Bioconductor
STAR enrichment analysis ( GSEA )
clusterProfiler
GitHub
R
GraphPad Prism

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis