Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity.
Open accessAbstract
It is now widely accepted, given the current weight of experimental evidence, that reactive oxygen species (ROS) contribute to cell and tissue dysfunction and damage caused by glucolipotoxicity in diabetes. The source of ROS in the insulin secreting pancreatic beta-cells and in the cells which are targets for insulin action has been considered to be the mitochondrial electron transport chain. While this source is undoubtably important, we provide additional information and evidence for NADPH oxidase-dependent generation of ROS both in pancreatic beta-cells and in insulin sensitive cells. While mitochondrial ROS generation may be important for regulation of mitochondrial uncoupling protein (UCP) activity and thus disruption of cellular energy metabolism, the NADPH oxidase associated ROS may alter parameters of signal transduction, insulin secretion, insulin action and cell proliferation or cell death. Thus NADPH oxidase may be a useful target for intervention strategies based on reversing the negative impact of glucolipotoxicity in diabetes.
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Chronically increased ROS production can induce β-cell death and result in gradual onset of diabetes.
“Chronically increased ROS production could also induce -cell death and result in gradual onset of diabetes (249 -253).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [251]
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New Insights into Fatty Acid Modulation of Pancreatic β‐Cell Function
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Time‐dependent effects of fatty acids on skeletal muscle metabolism
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Cell Culture Modeling to Test Therapies Against Hyperglycemia-Mediated Oxidative Stress and Injury
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Fatty acid-induced toxicity and neutral lipid accumulation in insulin-producing RINm5F cells
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PKCδ-mediated IRS-1 Ser24 phosphorylation negatively regulates IRS-1 function
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Endogenous islet uncoupling protein-2 expression and loss of glucose homeostasis in ob/ob mice
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The Activity of Leukocyte NADPH Oxidase: Regulation by p47 PHOX Cysteine and Serine Residues
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The Path to Insulin Resistance: Paved with Ceramides?
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Role of NADPH Oxidase and Calcium in Cerulein‐Induced Apoptosis
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- Authors
- Newsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira‐Emilio, H. C., Carpinelli, A. R., & Curi, R.
- Affiliations
- University College Dublin (IE)
- Hebrew University of Jerusalem (IL)
- Universidade de São Paulo (BR)
- Universidade Estadual de Ponta Grossa (BR)
- Corresponding author
- Newsholme, P.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2007-08
- Volume
- 583
- Issue
- 1
- Pages
- 9-24
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2277225
- OpenAlex
- W2164564813
- Cited by
- 684
- References
- 153
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 22 · 2023: 18 · 2022: 35 · 2021: 33 · 2020: 42 · 2019: 34 · 2018: 33 · 2017: 37 · 2016: 31 · 2015: 38 · 2014: 46 · 2013: 49 · 2012: 55
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Health Research Board
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- diabetes mellitus, reactive oxygen species, NADPH oxidase, mitochondrial reactive oxygen species, glucolipotoxicity, pancreatic beta cells, insulin secretion, insulin action, mitochondrial uncoupling proteins, cellular energy metabolism, signal transduction, cell proliferation, cell death
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Mitochondria, Apoptosis, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Insulin-Secreting Cells
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