Proteomics

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


ABSTRACT: Emerging evidence points towards an intricate relationship between the pandemic coronavirus disease 2019 (COVID-19) and diabetes. While diabetes is associated with an increased risk of severe COVID-19, new-onset type 1 diabetes (T1D) has been observed in COVID-19 patients, convoluting diabetes as both a risk factor and consequence of COVID-19. Understanding the mechanistic relationship between COVID-19 and T1D is an urgent and critical public health challenge. One pressing question is whether insulin-producing pancreatic β-cells can be infected by SARS-CoV-2, as T1D is a direct consequence of β-cell depletion. Here, we find that the SARS-CoV-2 receptor, ACE2 and its related entry factors, TMPRSS2, NRP1, and TRFC, are expressed in β-cells, with the latter two selectively present within β-cells. We discover that SARS-CoV-2 has selective cellular tropism for human pancreatic β-cells both ex vivo and in patients with COVID-19. We demonstrate that SARS-CoV-2 infection lowers the abundance of insulin within the pancreas, attenuates glucose-stimulated insulin secretion, and induces β-cell apoptosis. Finally, phosphoproteomic and pathway analysis suggests a SARS-CoV-2 stimulated signature for induction of apoptosis-associated signaling pathways in β-cells, similar to that seen in T1D. Taken together, our study demonstrates that SARS- CoV-2 can directly cause pancreatic islet impairment by killing β-cells, providing a mechanistic explanation for why T1D develops in COVID-19 patients.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Pancreatic Islet, Type B Pancreatic Cell

DISEASE(S): Insulinoma

SUBMITTER: Janos Demeter  

LAB HEAD: Jackson, Peter, K.

PROVIDER: PXD025629 | Pride | 2021-07-24

REPOSITORIES: Pride

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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 fact  ...[more]

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