Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns

Compelling evidence from earlier studies suggests that the pancreatic beta cell is inherently weak in its antioxidant defense mechanisms to face the burden of protecting itself against the increased intracellular oxidative stress following exposure to proinflammatory cytokines. Recent evidence impli...

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Autor principal: Kowluru, Anjaneyulu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759861/
https://www.ncbi.nlm.nih.gov/pubmed/33255484
http://dx.doi.org/10.3390/metabo10120480
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author Kowluru, Anjaneyulu
author_facet Kowluru, Anjaneyulu
author_sort Kowluru, Anjaneyulu
collection PubMed
description Compelling evidence from earlier studies suggests that the pancreatic beta cell is inherently weak in its antioxidant defense mechanisms to face the burden of protecting itself against the increased intracellular oxidative stress following exposure to proinflammatory cytokines. Recent evidence implicates novel roles for nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) as contributors to the excessive intracellular oxidative stress and damage under metabolic stress conditions. This review highlights the existing evidence on the regulatory roles of at least three forms of Noxs, namely Nox1, Nox2, and Nox4, in the cascade of events leading to islet beta cell dysfunction, specifically under the duress of chronic exposure to cytokines. Potential crosstalk between key signaling pathways (e.g., inducible nitric oxide synthase [iNOS] and Noxs) in the generation and propagation of reactive molecules and metabolites leading to mitochondrial damage and cell apoptosis is discussed. Available data accrued in investigations involving small-molecule inhibitors and antioxidant protein expression methods as tools toward the prevention of cytokine-induced oxidative damage are reviewed. Lastly, current knowledge gaps in this field, and possible avenues for future research are highlighted.
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spelling pubmed-77598612020-12-26 Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns Kowluru, Anjaneyulu Metabolites Review Compelling evidence from earlier studies suggests that the pancreatic beta cell is inherently weak in its antioxidant defense mechanisms to face the burden of protecting itself against the increased intracellular oxidative stress following exposure to proinflammatory cytokines. Recent evidence implicates novel roles for nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Noxs) as contributors to the excessive intracellular oxidative stress and damage under metabolic stress conditions. This review highlights the existing evidence on the regulatory roles of at least three forms of Noxs, namely Nox1, Nox2, and Nox4, in the cascade of events leading to islet beta cell dysfunction, specifically under the duress of chronic exposure to cytokines. Potential crosstalk between key signaling pathways (e.g., inducible nitric oxide synthase [iNOS] and Noxs) in the generation and propagation of reactive molecules and metabolites leading to mitochondrial damage and cell apoptosis is discussed. Available data accrued in investigations involving small-molecule inhibitors and antioxidant protein expression methods as tools toward the prevention of cytokine-induced oxidative damage are reviewed. Lastly, current knowledge gaps in this field, and possible avenues for future research are highlighted. MDPI 2020-11-24 /pmc/articles/PMC7759861/ /pubmed/33255484 http://dx.doi.org/10.3390/metabo10120480 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kowluru, Anjaneyulu
Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
title Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
title_full Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
title_fullStr Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
title_full_unstemmed Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
title_short Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns
title_sort oxidative stress in cytokine-induced dysfunction of the pancreatic beta cell: known knowns and known unknowns
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759861/
https://www.ncbi.nlm.nih.gov/pubmed/33255484
http://dx.doi.org/10.3390/metabo10120480
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