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Reactive oxygen species have a causal role in multiple forms of insulin resistance

Author

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  • Nicholas Houstis

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Whitehead Institute for Biomedical Research)

  • Evan D. Rosen

    (Broad Institute of MIT and Harvard
    Beth Israel Deaconess Medical Center)

  • Eric S. Lander

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Whitehead Institute for Biomedical Research
    Harvard Medical School)

Abstract

Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested1, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-α and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.

Suggested Citation

  • Nicholas Houstis & Evan D. Rosen & Eric S. Lander, 2006. "Reactive oxygen species have a causal role in multiple forms of insulin resistance," Nature, Nature, vol. 440(7086), pages 944-948, April.
    • Handle: RePEc:nat:nature:v:440:y:2006:i:7086:d:10.1038_nature04634
    DOI: 10.1038/nature04634
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    Cited by:

    1. Surapon Tangvarasittichai, 2018. "Iron Homeostasis and Diabetes Risk," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 7(4), pages 1-11, July.
    2. Yu Zou & Da-Hong Wang & Noriko Sakano & Yoshie Sato & Suketaka Iwanaga & Kazuhisa Taketa & Masayuki Kubo & Kei Takemoto & Chie Masatomi & Kiyomi Inoue & Keiki Ogino, 2014. "Associations of Serum Retinol, α-Tocopherol, and γ-Tocopherol with Biomarkers among Healthy Japanese Men," IJERPH, MDPI, vol. 11(2), pages 1-14, January.
    3. Hyo-Bum Kwak & Tracey L. Woodlief & Thomas D. Green & Julie H. Cox & Robert C. Hickner & P. Darrell Neufer & Ronald N. Cortright, 2019. "Overexpression of Long-Chain Acyl-CoA Synthetase 5 Increases Fatty Acid Oxidation and Free Radical Formation While Attenuating Insulin Signaling in Primary Human Skeletal Myotubes," IJERPH, MDPI, vol. 16(7), pages 1-15, March.
    4. Dustin W. Davis & Jeannette Crew & Petar Planinic & James M. Alexander & Arpita Basu, 2020. "Associations of Dietary Bioactive Compounds with Maternal Adiposity and Inflammation in Gestational Diabetes: An Update on Observational and Clinical Studies," IJERPH, MDPI, vol. 17(20), pages 1-21, October.
    5. Daniel J. Fazakerley & Julian van Gerwen & Kristen C. Cooke & Xiaowen Duan & Elise J. Needham & Alexis Díaz-Vegas & Søren Madsen & Dougall M. Norris & Amber S. Shun-Shion & James R. Krycer & James G. , 2023. "Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    6. Surapon Tangvarasittichai, 2018. "Iron Homeostasis and Diabetes Risk," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 7(4), pages 79-88, July.
    7. Natasha Chandiramani & Xianhong Wang & Marta Margeta, 2011. "Molecular Basis for Vulnerability to Mitochondrial and Oxidative Stress in a Neuroendocrine CRI-G1 Cell Line," PLOS ONE, Public Library of Science, vol. 6(1), pages 1-18, January.

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