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

Current Diabetes Reports

, Volume 13, Issue 2, pp 229-237

Epigenetics of Insulin Resistance: An Emerging Field in Translational Medicine

  • Silvia SookoianAffiliated withDepartment of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET)Instituto de Investigaciones Médicas A. Lanari-IDIM CONICET Email author 
  • , Carlos J. PirolaAffiliated withDepartment 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)

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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.

Keywords

Epigenetics DNA methylation Fatty liver NASH PPARGC1A PGC1a Insulin resistance Mitochondria Histones Acetylation Deacetylation Hypoxia Translational medicine