The first genome-scale DNA methylation study on pancreatic islets from type 2 diabetic patients identifies disease-associated DNA methylation pattern that translate into aberrant gene expression in novel factors relevant for β-cell function and survival

Bugliani, Marco

Calonne, Emilie

Cnop, Miriam

Cunha, Daniel A

Dedeurwaerder, Sarah

Defrance, Matthieu

Del Guerra, Silvia

Deplus, Rachel

Eizirik, Decio L

Fuks, François

Igoillo-Esteve, Mariana

Marchetti, Piero

Masini, Matilde

Naamane, Najib

Ndlovu, Matladi N

Volkmar, Michael

Volkmar, Ute

The EMBO Journal

English

PubMed

Michael Volkmar

Sarah Dedeurwaerder

Daniel A Cunha

Matladi N Ndlovu

Matthieu Defrance

Rachel Deplus

Emilie Calonne

Ute Volkmar

Mariana Igoillo-Esteve

Najib Naamane

Silvia Del Guerra

Matilde Masini

Marco Bugliani

Piero Marchetti

Miriam Cnop

Decio L Eizirik

François Fuks

Crossref

DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients

In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D and non-diabetic donors. We uncovered 276 CpG loci affiliated to promoters of 254 genes displaying significant differential DNA methylation in diabetic islets. These methylation changes were not present in blood cells from T2D individuals nor were they experimentally induced in non-diabetic islets by exposure to high glucose. For a subgroup of the differentially methylated genes, concordant transcriptional changes were present. Functional annotation of the aberrantly methylated genes and RNAi experiments highlighted pathways implicated in β-cell survival and function; some are implicated in cellular dysfunction while others facilitate adaptation to stressors. Together, our findings offer new insights into the intricate mechanisms of T2D pathogenesis, underscore the important involvement of epigenetic dysregulation in diabetic islets and may advance our understanding of T2D aetiology

Volkmar M

Dedeurwaerder S

Cunha DA

Ndlovu MN

Defrance M

Deplus R

Calonne E

Volkmar U

Igoillo Esteve M

Naamane N

Cnop M

Eizirik DL

Fuks F.

DEL GUERRA, SILVIA

MASINI, MATILDE

BUGLIANI, MARCO

MARCHETTI, PIERO

Archivio della Ricerca - Università di Pisa

In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D and non-diabetic donors. We uncovered 276 CpG loci affiliated to promoters of 254 genes displaying significant differential DNA methylation in diabetic islets. These methylation changes were not present in blood cells from T2D individuals nor were they experimentally induced in non-diabetic islets by exposure to high glucose. For a subgroup of the differentially methylated genes, concordant transcriptional changes were present. Functional annotation of the aberrantly methylated genes and RNAi experiments highlighted pathways implicated in β-cell survival and function; some are implicated in cellular dysfunction while others facilitate adaptation to stressors. Together, our findings offer new insights into the intricate mechanisms of T2D pathogenesis, underscore the important involvement of epigenetic dysregulation in diabetic islets and may advance our understanding of T2D aetiology.info:eu-repo/semantics/publishe

Andrade Da Cunha, Daniel

Ndlovu, Matladi N.

Igoillo Esteve, Mariana

Eizirik, Decio L.

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DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients.

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DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients

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Archivio della Ricerca - Università di Pisa

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