Epigenetic changes in diabetes

Authors

  • ST Keating,

    1. Epigenetics in Human Health and Disease Laboratory
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  • A El-Osta

    Corresponding author
    1. Epigenomics Profiling Facility, Baker IDI Heart & Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia
    2. Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia
    3. Central Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia
    • Epigenetics in Human Health and Disease Laboratory
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  • The authors report no conflicts of interest.

Corresponding author: Assam El-Osta, Epigenomics Profiling Facility, Baker IDI Heart & Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria 3004, Australia.

Tel.: 613 85321389

fax: 613 85321100

e-mail: assam.el-osta@bakeridi.edu.au

Abstract

Diabetes is a multifactorial disease with numerous pathways influencing its progression and recent observations suggest that the complexity of the disease cannot be entirely accounted for by genetic predisposition. A compelling argument for an epigenetic component is rapidly emerging. Epigenetic processes at the chromatin template significantly sensitize transcriptional and phenotypic outcomes to environmental signaling information including metabolic state, nutritional requirements and history. Epigenetic mechanisms impact gene expression that could predispose individuals to the diabetic phenotype during intrauterine and early postnatal development, as well as throughout adult life. Furthermore, epigenetic changes could account for the accelerated rates of chronic and persistent microvascular and macrovascular complications associated with diabetes. Epidemiological and experimental animal studies identified poor glycemic control as a major contributor to the development of diabetic complications and highlight the requirement for early intervention. Early exposure to hyperglycemia can drive the development of complications that manifest late in the progression of the disease and persist despite improved glycemic control, indicating a memory of the metabolic insult. Understanding the molecular events that underlie these transcriptional changes will significantly contribute to novel therapeutic interventions to prevent, reverse or retard the deleterious effects of the diabetic milieu.

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