Cited by 878Redox biology and oxidative stressAntioxidant Activity and Oxidative StressNitric Oxide and Endothelin Effects

Molecular mechanisms of ROS production and oxidative stress in diabetes

Newsholme, Philip, Cruzat, Vinicius Fernandes, Keane, Kevin Noel, Carlessi, Rodrigo, de Bittencourt, Paulo Ivo Homem·2016·Biochemical Journal

Abstract

Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation

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Crossref · 10.1042/bcj20160503c

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  • With the destruction of β cells, the peak of insulin secretion will be delayed, intensifying the fluctuation of blood glucose, resulting in further severe damage of β cells.

    “With the destruction of β cells, the peak of insulin secretion will be delayed, intensifying the fluctuation of blood glucose, resulting in further severe damage of β cells (85).”

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Authors
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H.
Affiliations
  • Curtin University (AU)
  • School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Kent St., Bentley, Perth, Western Australia 6102, Australia
  • Laboratory of Cellular Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil
Venue
Biochemical Journal
Published
2016-12-09
Volume
473
Issue
24
Pages
4527-4550
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W2560781586
Cited by
878
References
261
Citations by year
2026: 64 · 2025: 76 · 2024: 103 · 2023: 102 · 2022: 124 · 2021: 136 · 2020: 125 · 2019: 67 · 2018: 41 · 2017: 38 · 2015: 1
FWCI
4.40
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed (publishedVersion)
  • eSpace (Curtin University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
reactive oxygen species, oxidative stress, diabetes mellitus, insulin resistance, insulin secretion, redox regulation, chronic inflammation, obesity, lipid peroxidation, protein carbonylation, antioxidant status, high-fat diet, physical activity
MeSH terms
Animals, Diabetes Mellitus, Humans, Insulin, Reactive Oxygen Species, Oxidative Stress, Insulin-Secreting Cells

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