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

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Bacos , K , Gillberg , L , Volkov , P , Olsson , A H , Hansen , T , Pedersen , O , Gjesing , A P , Eiberg , H , Tuomi , T , Almgren , P , Groop , L , Eliasson , L , Vaag , A , Dayeh , T & Ling , C 2016 , ' Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes ' Nature Communications , vol. 7 , 11089 . DOI: 10.1038/ncomms11089

Title: Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
Author: Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H.; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-03
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/161324
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 beta-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.
Subject: HUMAN PANCREATIC-ISLETS
HUMAN SKELETAL-MUSCLE
WIDE DNA METHYLATION
GENE-EXPRESSION
DECREASED EXPRESSION
ADIPOSE-TISSUE
BETA-CELL
TYPE-2
MICROARRAY
MELLITUS
3121 Internal medicine
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