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

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 methylati...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821875/
https://www.ncbi.nlm.nih.gov/pubmed/27029739
http://dx.doi.org/10.1038/ncomms11089
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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
author_facet 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
author_sort Bacos, Karl
collection PubMed
description 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.
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spelling pubmed-48218752016-04-17 Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes 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 Nat Commun Article 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. Nature Publishing Group 2016-03-31 /pmc/articles/PMC4821875/ /pubmed/27029739 http://dx.doi.org/10.1038/ncomms11089 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
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
Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
title Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
title_full Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
title_fullStr Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
title_full_unstemmed Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
title_short Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
title_sort blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821875/
https://www.ncbi.nlm.nih.gov/pubmed/27029739
http://dx.doi.org/10.1038/ncomms11089
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