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Epigenetic changes in islets of langerhans preceding the onset of diabetes

Ouni, Meriem ; Saussenthaler, Sophie ; Eichelmann, Fabian ; Jähnert, Markus ; Stadion, Mandy ; Wittenbecher, Clemens ; Rönn, Tina LU ; Zellner, Lisa ; Gottmann, Pascal and Ling, Charlotte LU , et al. (2020) In Diabetes 69(11). p.2503-2517
Abstract

The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for pre-vention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident... (More)

The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for pre-vention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
69
issue
11
pages
15 pages
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85092592760
  • pmid:32816961
ISSN
0012-1797
DOI
10.2337/db20-0204
language
English
LU publication?
yes
id
2cecdf24-eaeb-4d5a-b0a7-47e54f2fde34
date added to LUP
2020-11-05 13:27:17
date last changed
2021-02-23 04:37:48
@article{2cecdf24-eaeb-4d5a-b0a7-47e54f2fde34,
  abstract     = {<p>The identification of individuals with a high risk of developing type 2 diabetes (T2D) is fundamental for pre-vention. Here, we used a translational approach and prediction criteria to identify changes in DNA methylation visible before the development of T2D. Islets of Langerhans were isolated from genetically identical 10-week-old female New Zealand Obese mice, which differ in their degree of hyperglycemia and in liver fat content. The application of a semiexplorative approach identified 497 differentially expressed and methylated genes (P = 6.42e-09, hypergeometric test) enriched in pathways linked to insulin secretion and extracellular matrix-receptor interaction. The comparison of mouse data with DNA methylation levels of incident T2D cases from the prospective European Prospective Investigation of Cancer (EPIC)-Potsdam cohort, revealed 105 genes with altered DNA methylation at 605 cytosine-phosphate-guanine (CpG) sites, which were associated with future T2D. AKAP13, TENM2, CTDSPL, PTPRN2, and PTPRS showed the strongest predictive potential (area under the receiver operating characteristic curve values 0.62–0.73). Among the new candidates identified in blood cells, 655 CpG sites, located in 99 genes, were differentially methylated in islets of humans with T2D. Using correction for multiple testing detected 236 genes with an altered DNA methylation in blood cells and 201 genes in diabetic islets. Thus, the introduced translational approach identified novel putative biomarkers for early pancreatic islet aberrations preceding T2D.</p>},
  author       = {Ouni, Meriem and Saussenthaler, Sophie and Eichelmann, Fabian and Jähnert, Markus and Stadion, Mandy and Wittenbecher, Clemens and Rönn, Tina and Zellner, Lisa and Gottmann, Pascal and Ling, Charlotte and Schulze, Matthias B. and Schürmann, Annette},
  issn         = {0012-1797},
  language     = {eng},
  number       = {11},
  pages        = {2503--2517},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Epigenetic changes in islets of langerhans preceding the onset of diabetes},
  url          = {http://dx.doi.org/10.2337/db20-0204},
  doi          = {10.2337/db20-0204},
  volume       = {69},
  year         = {2020},
}