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Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes

Author

Listed:
  • Karl Bacos

    (Epigenetics and Diabetes Unit, Lund University Diabetes Centre)

  • Linn Gillberg

    (Diabetes and Metabolism, Rigshospitalet
    Faculty of Health Sciences, University of Copenhagen)

  • Petr Volkov

    (Epigenetics and Diabetes Unit, Lund University Diabetes Centre)

  • Anders H Olsson

    (Diabetes and Metabolism, Rigshospitalet)

  • Torben Hansen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen)

  • Oluf Pedersen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen)

  • Anette Prior Gjesing

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen)

  • Hans Eiberg

    (Faculty of Health and Medical Sciences, University of Copenhagen)

  • Tiinamaija Tuomi

    (Abdominal Centre, Helsinki University Hospital
    Folkhalsan Research Center
    Finnish Institute for Molecular Medicine, University of Helsinki)

  • Peter Almgren

    (Diabetes and Endocrinology, Lund University Diabetes Centre)

  • Leif Groop

    (Finnish Institute for Molecular Medicine, University of Helsinki
    Diabetes and Endocrinology, Lund University Diabetes Centre)

  • Lena Eliasson

    (Islet cell exocytosis, Lund University Diabetes Centre)

  • Allan Vaag

    (Diabetes and Metabolism, Rigshospitalet
    Faculty of Health Sciences, University of Copenhagen)

  • Tasnim Dayeh

    (Epigenetics and Diabetes Unit, Lund University Diabetes Centre)

  • Charlotte Ling

    (Epigenetics and Diabetes Unit, Lund University Diabetes Centre)

Abstract

Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26–74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in β-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.

Suggested Citation

  • Karl Bacos & Linn Gillberg & Petr Volkov & Anders H Olsson & Torben Hansen & Oluf Pedersen & Anette Prior Gjesing & Hans Eiberg & Tiinamaija Tuomi & Peter Almgren & Leif Groop & Lena Eliasson & Allan , 2016. "Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11089
    DOI: 10.1038/ncomms11089
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    Cited by:

    1. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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