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Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets.


ABSTRACT: Pancreatic islets of type 2 diabetes patients have altered DNA methylation, contributing to islet dysfunction and the onset of type 2 diabetes. The cause of these epigenetic alterations is largely unknown. We set out to test whether (i) islet DNA methylation would change with aging and (ii) early postnatal overnutrition would persistently alter DNA methylation. We performed genome-scale DNA methylation profiling in islets from postnatally over-nourished (suckled in a small litter) and control male mice at both postnatal day 21 and postnatal day 180. DNA methylation differences were validated using quantitative bisulfite pyrosequencing, and associations with expression were assessed by RT-PCR. We discovered that genomic regions that are hypermethylated in exocrine relative to endocrine pancreas tend to gain methylation in islets during aging (R 2 = 0.33, P?

SUBMITTER: Li G 

PROVIDER: S-EPMC6735752 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Early postnatal overnutrition accelerates aging-associated epigenetic drift in pancreatic islets.

Li Ge G   Petkova Tihomira D TD   Laritsky Eleonora E   Kessler Noah N   Baker Maria S MS   Zhu Shaoyu S   Waterland Robert A RA  

Environmental epigenetics 20190701 3


Pancreatic islets of type 2 diabetes patients have altered DNA methylation, contributing to islet dysfunction and the onset of type 2 diabetes. The cause of these epigenetic alterations is largely unknown. We set out to test whether (i) islet DNA methylation would change with aging and (ii) early postnatal overnutrition would persistently alter DNA methylation. We performed genome-scale DNA methylation profiling in islets from postnatally over-nourished (suckled in a small litter) and control ma  ...[more]

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