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Diabetologia
Published in: Diabetologia 3/2016

Open Access 01-03-2016 | Article

Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets

Authors: Ionel Sandovici, Constanze M. Hammerle, Wendy N. Cooper, Noel H. Smith, Jane L. Tarry-Adkins, Benjamin J. Dunmore, Julien Bauer, Simon R. Andrews, Giles S. H. Yeo, Susan E. Ozanne, Miguel Constância

Published in: Diabetologia | Issue 3/2016

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Abstract

Aims/hypothesis

Ageing is a major risk factor for development of metabolic diseases such as type 2 diabetes. Identification of the mechanisms underlying this association could help to elucidate the relationship between age-associated progressive loss of metabolic health and development of type 2 diabetes. We aimed to determine molecular signatures during ageing in the endocrine pancreas.

Methods

Global gene transcription was measured in pancreatic islets isolated from young and old rats by Ilumina BeadChip arrays. Promoter DNA methylation was measured by Sequenom MassArray in 46 genes that showed differential expression with age, and correlations with expression were established. Alterations in morphological and cellular processes with age were determined by immunohistochemical methods.

Results

Age-related changes in gene expression were found at 623 loci (>1.5-fold, false discovery rate [FDR] <5%), with a significant (FDR < 0.05) enrichment in genes previously implicated in islet-cell function (Enpp1, Abcc8), type 2 diabetes (Tspan8, Kcnq1), inflammatory processes (Cxcl9, Il33) and extracellular matrix organisation (Col3a1, Dpt). Age-associated transcriptional differences negatively correlated with promoter DNA methylation at several loci related to inflammation, glucose homeostasis, cell proliferation and cell–matrix interactions (Il33, Cxcl9, Gpr119, Fbp2, Col3a1, Dpt, Spp1).

Conclusions/interpretation

Our findings suggest that a significant proportion of pancreatic islets develop a low-grade ‘chronic’ inflammatory status with ageing and this may trigger altered functional plasticity. Furthermore, we identified changes in expression of genes previously linked to type 2 diabetes and associated changes in DNA methylation that could explain their age-associated dysregulation. These findings provide new insights into key (epi)genetic signatures of the ageing process in islets.
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Metadata
Title
Ageing is associated with molecular signatures of inflammation and type 2 diabetes in rat pancreatic islets
Authors
Ionel Sandovici
Constanze M. Hammerle
Wendy N. Cooper
Noel H. Smith
Jane L. Tarry-Adkins
Benjamin J. Dunmore
Julien Bauer
Simon R. Andrews
Giles S. H. Yeo
Susan E. Ozanne
Miguel Constância
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 3/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3837-8

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