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

作者：Akirav Eitan M; Lebastchi Jasmin; Galvan Eva M; Henegariu Octavian; Akirav Michael; Ablamunits Vitaly; Lizardi Paul M; Herold Kevan C^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(47): 19018-19023.

DOI：10.1073/pnas.1111008108

• epigenetics
• autoimmunity
• biomarker

In diabetes mellitus, beta cell destruction is largely silent and can be detected only after significant loss of insulin secretion capacity. We have developed a method for detecting beta cell death in vivo by amplifying and measuring the proportion of insulin 1 DNA from beta cells in the serum. By using primers that are specific for DNAmethylation patterns in beta cells, we have detected circulating copies of beta cell-derived demethylated DNA in serum of mice by quantitative PCR. Accordingly, we have identified a relative increase of beta 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 beta 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 beta cell death in vivo that may be used to track the progression of diabetes and guide its treatment.

• 出版日期2011-11-22