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

Imagen de Paul Lizardi
PDF versionPDF version
TítuloDetection of β cell death in diabetes using differentially methylated circulating DNA.
Publication TypeJournal Article
Year of Publication2011
AutoresAkirav, EM, Lebastchi, J, Galvan, EM, Henegariu, O, Akirav, M, Ablamunits, V, Lizardi, PM, Herold, KC
JournalProc Natl Acad Sci U S A
Volume108
Issue47
Pagination19018-23
Date Published2011 Nov 22
ISSN1091-6490
Palabras claveAnimals, Base Sequence, Cell Death, Cloning, Molecular, Diabetes mellitus, DNA, DNA Primers, Female, Fluorescent Antibody Technique, Humans, Insulin, Insulin-Secreting Cells, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Molecular Sequence Data, Monitoring, Physiologic, Real-Time Polymerase Chain Reaction, Sequence Analysis, DNA
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 DNA methylation 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.

DOI10.1073/pnas.1111008108
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22074781
PubMed Central IDPMC3223447
Grant ListP30 DK45735 / DK / NIDDK NIH HHS / United States
UL1RR024139 / RR / NCRR NIH HHS / United States