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Translational implications of the β-cell epigenome in diabetes mellitus

  • Justin S. Johnson
    Affiliations
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Ind
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  • Carmella Evans-Molina
    Correspondence
    Reprint requests: Carmella Evans-Molina, Richard L. Roudebush Veterans Affairs Medical Center, Indiana University School of Medicine, 635 Barnhill Drive, MS2031A, Indianapolis, IN 46202
    Affiliations
    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Ind

    Department of Medicine, Indiana University School of Medicine, Indianapolis, Ind

    Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Ind

    Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind

    Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, Ind
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Published:March 14, 2014DOI:https://doi.org/10.1016/j.trsl.2014.03.002
      Diabetes mellitus is a disorder of glucose homeostasis that affects more than 24 million Americans and 382 million individuals worldwide. Dysregulated insulin secretion from the pancreatic β cells plays a central role in the pathophysiology of all forms of diabetes mellitus. Therefore, an enhanced understanding of the pathways that contribute to β-cell failure is imperative. Epigenetics refers to heritable changes in DNA transcription that occur in the absence of changes to the linear DNA nucleotide sequence. Recent evidence suggests an expanding role of the β-cell epigenome in the regulation of metabolic health. The goal of this review is to discuss maladaptive changes in β-cell DNA methylation patterns and chromatin architecture, and their contribution to diabetes pathophysiology. Efforts to modulate the β-cell epigenome as a means to prevent, diagnose, and treat diabetes are also discussed.

      Abbreviations:

      Arx (arista-less-related homeobox protein), CDK5 (cyclin-dependent kinase 5), CpG (Cytosine-phosphodiester-bond-guanine), DM (diabetes mellitus), EZH2 (enhancer of zeste homolog 2), GLP-1 (glucagonlike peptide 1), GWAS (genomewide association study), H3-K4 (Lys-4 dimethylation of histone H3), HAT (histone acetyltransferase protein), HDAC (histone deacetylase protein), HDACi (histone deacetylase protein inhibitor), HMT (histone methyltransferase), IUGR (intrauterine growth restriction), LSD-1 (lysine-specific demethylase 1), Lys (lysine), MAOI (monoamine oxidase inhibitor), NOD (nonobese diabetic), Pax4 (paired box 4), Pdx-1 (pancreatic and duodenal homeobox 1), SET (Su(var)3-9 and enhancer of zeste), SNP (single nucleotide polymorphism), T1D (type 1 diabetes), T2D (type 2 diabetes), TND (transient neonatal diabetes), VPA (valproic acid)
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