Sommese Linda, Zullo Alberto, Mancini Francesco Paolo, Fabbricini Rossella, Soricelli Andrea, Napoli Claudio
a U.O.C. Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology, Regional Reference Laboratory of Transplant Immunology , Department of Internal and Specialty Medicine , Azienda Ospedaliera Universitaria (AOU), Università degli Studi della Campania "Luigi Vanvitelli ," Italy.
b Department of Experimental Medicine , Second University of Naples , Italy.
Epigenetics. 2017 Jun 3;12(6):401-415. doi: 10.1080/15592294.2016.1278097. Epub 2017 Jan 6.
Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.
表观遗传学参与了构成胰岛素抵抗和功能不全基础的基因网络的表达改变。控制β细胞分化和功能的主要基因，如PAX4、PDX1和胰高血糖素样肽-1受体，都受到表观遗传的调控。表观遗传学可通过与多种因素（如核因子κB、骨桥蛋白和Toll样受体）相关的免疫介导的促炎作用导致胰岛素抵抗。在此，我们对该主题进行了批判性和全面的总结，特别强调了转化医学和临床方面。我们讨论了表观遗传学对用于细胞替代治疗的β细胞再生的影响、用于分析表观遗传学对2型糖尿病（T2DM）贡献的新兴生物信息学方法、T2DM中跨代遗传假说的表观遗传核心以及T2DM的表观遗传学临床试验。因此，预防或逆转T2DM发生过程中出现的表观遗传变化可能会减轻该疾病对个人和社会的负担。
