SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment
| العنوان: | SARS-CoV-2 infects human pancreatic β cells and elicits β cell impairment |
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| المؤلفون: | Peter K. Jackson, Peter V. Lidsky, Matthias S. Matter, Bokai Zhu, Anna K. Stalder, Yinghong Xiao, Jayakar V. Nayak, Garry P. Nolan, Raul Andino, Ivan T. Lee, Sizun Jiang, Yury Goltsev, Chien-Ting Wu, Han Chen, Romina J. Bevacqua, Robert L. Whitener, Janos Demeter, Charles A. Chang, Ran Cheng, Tsuguhisa Nakayama, Alexandar Tzankov |
| المصدر: | Cell Metabolism Cell metabolism, vol 33, iss 8 |
| بيانات النشر: | Elsevier Inc., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Physiology, type 1 diabetes, Cell, ACE2, Apoptosis, Medical Biochemistry and Metabolomics, neuropilin 1, 0302 clinical medicine, Insulin-Secreting Cells, Receptors, 80 and over, Insulin, 2.1 Biological and endogenous factors, Aetiology, Receptor, Lung, Serine Endopeptidases, Diabetes, Transferrin, apoptosis, phosphoproteomics, Middle Aged, Spike Glycoprotein, Virus, CD, SARS-CoV-2 spike protein, Cell killing, medicine.anatomical_structure, Infectious Diseases, Host-Pathogen Interactions, Pneumonia & Influenza, Female, Angiotensin-Converting Enzyme 2, Adult, Cell signaling, insulin, Biology, Autoimmune Disease, 03 medical and health sciences, Endocrinology & Metabolism, Clinical Research, medicine, Diabetes Mellitus, Humans, Secretion, Antigens, Molecular Biology, Metabolic and endocrine, Aged, A549 cell, Type 1 diabetes, SARS-CoV-2, Prevention, fungi, COVID-19, Cell Biology, Pneumonia, Virus Internalization, Clinical and Translational Report, medicine.disease, Neuropilin-1, Coronavirus, 030104 developmental biology, Emerging Infectious Diseases, Good Health and Well Being, A549 Cells, Case-Control Studies, Cancer research, pancreatic beta cell, Biochemistry and Cell Biology, Apoptosis Regulatory Proteins, 030217 neurology & neurosurgery |
| الوصف: | 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. Graphical abstract Diabetic patients are at risk for severe COVID-19, but the virus may further damage insulin-secreting β cells. Wu et al. found that patient β cells are virally infected and the highly expressed neuropilin-1 receptor is critical for viral entry, causing cell death and reduced insulin secretion, exacerbating diabetes in patients. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-7420 1550-4131 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::29dfd8b903035a419ccf9d57cbd7e975Test http://europepmc.org/articles/PMC8130512Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....29dfd8b903035a419ccf9d57cbd7e975 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19327420 15504131 |
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