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Diabetes and susceptibility to infections: Implication for COVID‐19

A number of mechanisms have been proposed to explain the well‐established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID‐19 infections. Though it has long been note...

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Autores principales: van Niekerk, Gustav, van der Merwe, Michelle, Engelbrecht, Anna‐Mart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446942/
https://www.ncbi.nlm.nih.gov/pubmed/34115881
http://dx.doi.org/10.1111/imm.13383
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author van Niekerk, Gustav
van der Merwe, Michelle
Engelbrecht, Anna‐Mart
author_facet van Niekerk, Gustav
van der Merwe, Michelle
Engelbrecht, Anna‐Mart
author_sort van Niekerk, Gustav
collection PubMed
description A number of mechanisms have been proposed to explain the well‐established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID‐19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune‐related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID‐19 infections.
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spelling pubmed-84469422021-09-17 Diabetes and susceptibility to infections: Implication for COVID‐19 van Niekerk, Gustav van der Merwe, Michelle Engelbrecht, Anna‐Mart Immunology Reviews A number of mechanisms have been proposed to explain the well‐established link between diabetic status and an increased susceptibility to infection. Notably, diabetes has been shown to be one of the strongest factors influencing healthcare outcome in COVID‐19 infections. Though it has long been noted that lymphocytes upregulate insulin receptors following immune activation, until recently, this observation has received little attention. Here, we point out key findings implicating dysregulated insulin signalling in immune cells as a possible contributing factor in the immune pathology associated with diabetes. Mechanistically, insulin, by activating the PI3K/Akt/mTOR pathway, regulates various aspects of both myeloid cells and lymphocytes, such as cell survival, metabolic reprogramming and the polarization and differentiation of immune cells. PI3K signalling is also supressed by immune checkpoint proteins, suggesting that insulin signalling may antagonize peripheral tolerance. Remarkably, it has also recently been shown that, following insulin binding, the insulin receptor translocates to the nucleus where it plays a key role in regulating the transcription of various immune‐related genes, including pathways involved in viral infections. Taken together, these observations suggest that dysregulated insulin signalling may directly contribute to a defective immune response during COVID‐19 infections. John Wiley and Sons Inc. 2021-06-24 2021-11 /pmc/articles/PMC8446942/ /pubmed/34115881 http://dx.doi.org/10.1111/imm.13383 Text en © 2021 John Wiley & Sons Ltd
spellingShingle Reviews
van Niekerk, Gustav
van der Merwe, Michelle
Engelbrecht, Anna‐Mart
Diabetes and susceptibility to infections: Implication for COVID‐19
title Diabetes and susceptibility to infections: Implication for COVID‐19
title_full Diabetes and susceptibility to infections: Implication for COVID‐19
title_fullStr Diabetes and susceptibility to infections: Implication for COVID‐19
title_full_unstemmed Diabetes and susceptibility to infections: Implication for COVID‐19
title_short Diabetes and susceptibility to infections: Implication for COVID‐19
title_sort diabetes and susceptibility to infections: implication for covid‐19
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446942/
https://www.ncbi.nlm.nih.gov/pubmed/34115881
http://dx.doi.org/10.1111/imm.13383
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