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Epigenetics of Insulin Resistance: An Emerging Field in Translational Medicine

  • Pathogenesis of Type 2 Diabetes and Insulin Resistance (RM Watanabe, Section Editor)
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Abstract

In this article, we review the current knowledge of and recent insights into the role of epigenetic factors in the development of insulin resistance (IR), with emphasis on peroxisome proliferator-activated receptor gamma coactivator 1α (PPARGC1A or PGC1α) methylation on fetal programming and liver modulation of glucose-related phenotypes. We discuss the pathogenesis of IR beyond the integrity of β-cell function and illustrate the novel concept of mitochondrial epigenetics to explain the pathobiology of metabolic-syndrome-related phenotypes. Moreover, we discuss whether epigenetic marks in genes of the circadian rhythm system are able to modulate insulin/glucose-related metabolic functions and place hypoxia inducible factor 1 α (HIF1α) as a part of the master CLOCK gene/protein interaction network that might modulate IR. Finally, we highlight relevant information about epigenetic marks and IR so that clinicians practicing in the community may envision future areas of medical intervention and predict putative biomarkers for early disease detection.

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Acknowledgment

This study was partially supported by Grants PICT 2008–1521 and PICT 2010–0441 (Agencia Nacional de Promoción Científica y Tecnológica) and UBACYT CM04 (Universidad de Buenos Aires). S.S. and C.J.P. belong to Consejo Nacional de Investigaciones Científicas (CONICET).

Disclosure

Conflicts of interest: S. Sookoian: none; C.J. Pirola: has board membership with Merck Sharp and Dohme, has given expert testimony for Merck Sharp and Dohme, and has received grant support and honoraria from Merck Sharp and Dohme.

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Authors and Affiliations

  1. Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Silvia Sookoian

  2. Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National-Council of Scientific and Technological Research (CONICET), Ciudad Autónoma de Buenos Aires, Argentina

    Carlos J. Pirola

  3. Instituto de Investigaciones Médicas A. Lanari-IDIM CONICET, Combatiente de Malvinas 3150, Buenos Aires, 1427, Argentina

    Silvia Sookoian

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  1. Silvia Sookoian
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  2. Carlos J. Pirola
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Correspondence to Silvia Sookoian.

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Sookoian, S., Pirola, C.J. Epigenetics of Insulin Resistance: An Emerging Field in Translational Medicine. Curr Diab Rep 13, 229–237 (2013). https://doi.org/10.1007/s11892-012-0361-9

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