DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients.
DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients.
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DOI：
10.1038/emboj.2011.503
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发表时间：
2012-03-21
期刊：
影响因子：
11.4
通讯作者：
Fuks, Francois
中科院分区：
文献类型：
--
作者：
Volkmar, Michael;Dedeurwaerder, Sarah;Cunha, Daniel A.;Ndlovu, Matladi N.;Defrance, Matthieu;Deplus, Rachel;Calonne, Emilie;Volkmar, Ute;Igoillo-Esteve, Mariana;Naamane, Najib;Del Guerra, Silvia;Masini, Matilde;Bugliani, Marco;Marchetti, Piero;Cnop, Miriam;Eizirik, Decio L.;Fuks, Francois
除了遗传倾向外，环境和生活方式因素也会导致 2 型糖尿病 (T2D) 的发病。表观遗传变化可能为将环境暴露转化为病理机制提供了联系。在这项研究中，我们首次对 T2D 和非糖尿病供体的胰岛进行了全面的 DNA 甲基化分析。我们发现了 276 个 CpG 位点，它们隶属于 254 个基因的启动子，在糖尿病胰岛中显示出显着差异的 DNA 甲基化。这些甲基化变化不存在于 T2D 个体的血细胞中，也不是通过暴露于高葡萄糖而在非糖尿病胰岛中实验诱导的。对于差异甲基化基因的一个亚组，存在一致的转录变化。异常甲基化基因的功能注释和 RNAi 实验强调了与 β 细胞存活和功能有关的途径；有些与细胞功能障碍有关，而另一些则有助于适应压力源。总之，我们的研究结果为 T2D 发病机制的复杂机制提供了新的见解，强调了表观遗传失调在糖尿病胰岛中的重要参与，并可能增进我们对 T2D 病因学的理解。
In addition to genetic predisposition, environmental and lifestyle factors contribute to the pathogenesis of type 2 diabetes (T2D). Epigenetic changes may provide the link for translating environmental exposures into pathological mechanisms. In this study, we performed the first comprehensive DNA methylation profiling in pancreatic islets from T2D and non-diabetic donors. We uncovered 276 CpG loci affiliated to promoters of 254 genes displaying significant differential DNA methylation in diabetic islets. These methylation changes were not present in blood cells from T2D individuals nor were they experimentally induced in non-diabetic islets by exposure to high glucose. For a subgroup of the differentially methylated genes, concordant transcriptional changes were present. Functional annotation of the aberrantly methylated genes and RNAi experiments highlighted pathways implicated in β-cell survival and function; some are implicated in cellular dysfunction while others facilitate adaptation to stressors. Together, our findings offer new insights into the intricate mechanisms of T2D pathogenesis, underscore the important involvement of epigenetic dysregulation in diabetic islets and may advance our understanding of T2D aetiology.
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影响因子：
4.8
作者：
Cnop, Miriam;Ladriere, Laurence;Eizirik, Decio L.
通讯作者：
Eizirik, Decio L.
影响因子：
2.7
作者：
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作者：
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影响因子：
6.7
作者：
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通讯作者：
Mastronardi, Fabrizio