Detection of β cell death in diabetes using differentially methylated circulating DNA

Eitan M. Akirav, Jasmin Lebastchi, Eva M. Galvan, Octavian Henegariu, Michael Akirav, Vitaly Ablamunits, Paul M. Lizardi, Kevan C. Herold

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

In diabetes mellitus, β cell destruction is largely silent and can be detected only after significant loss of insulin secretion capacity. We have developed a method for detecting β cell death in vivo by amplifying and measuring the proportion of insulin 1 DNA from β cells in the serum. By using primers that are specific for DNAmethylation patterns in β cells, we have detected circulating copies of β cell-derived demethylated DNA in serum of mice by quantitative PCR. Accordingly, we have identified a relative increase of β cell-derived DNA after induction of diabetes with streptozotocin and during development of diabetes in nonobese diabetic mice. We have extended the use of this assay to measure β cell-derived insulin DNA in human tissues and serum. We found increased levels of demethylated insulin DNA in subjects with new-onset type 1 diabetes compared with age-matched control subjects. Our method provides a noninvasive approach for detecting β cell death in vivo that may be used to track the progression of diabetes and guide its treatment.

Original languageEnglish (US)
Pages (from-to)19018-19023
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number47
DOIs
StatePublished - Nov 22 2011
Externally publishedYes

Keywords

  • Autoimmunity
  • Biomarker
  • Epigenetics

ASJC Scopus subject areas

  • General

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