Detection of β cell death in diabetes using differentially methylated circulating DNA.
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Title | Detection of β cell death in diabetes using differentially methylated circulating DNA. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Akirav, EM, Lebastchi, J, Galvan, EM, Henegariu, O, Akirav, M, Ablamunits, V, Lizardi, PM, Herold, KC |
Journal | Proc Natl Acad Sci U S A |
Volume | 108 |
Issue | 47 |
Pagination | 19018-23 |
Date Published | 2011 Nov 22 |
ISSN | 1091-6490 |
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. |
DOI | 10.1073/pnas.1111008108 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 22074781 |
PubMed Central ID | PMC3223447 |
Grant List | P30 DK45735 / DK / NIDDK NIH HHS / United States UL1RR024139 / RR / NCRR NIH HHS / United States |