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与2型糖尿病发病机制相关的表观遗传修饰

Epigenetic Modifications Associated with the Pathogenesis of Type 2 Diabetes Mellitus.

作者信息

Hossan Tareq, Kundu Shoumik, Alam Sayeda Sadia, Nagarajan Sankari

机构信息

Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka-1342, Bangladesh.

Cancer Research UK Cambridge Institute (CRUK-CI), University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, United Kingdom.

出版信息

Endocr Metab Immune Disord Drug Targets. 2019;19(6):775-786. doi: 10.2174/1871530319666190301145545.

Abstract

BACKGROUND AND OBJECTIVE

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder. Pancreatic β-cell dysfunction and insulin resistance are the most common and crucial events of T2DM. Increasing evidence suggests the association of epigenetic modifications with the pathogenesis of T2DM through the changes in important biological processes including pancreatic β- cell differentiation, development and maintenance of normal β-cell function. Insulin sensitivity by the peripheral glucose uptake tissues is also changed by the altered epigenetic mechanisms. In this review, we discussed the major epigenetic alterations and their effects on β-cell function, insulin secretion and insulin resistance in context of T2DM.

METHODS

We investigated the presently available epigenetic modifications including DNA methylation, posttranslational histone modifications, ATP-dependent chromatin remodeling and non-coding RNAs related to the pathogenesis of T2DM. Published literatures on this topic were searched both on Google Scholar and Pubmed with related keywords and investigated for relevant information.

RESULTS

The epigenetic modifications introduce changes in gene expression which are essential for appropriate β-cell development and functions, insulin secretion and sensitivity resulting in the pathogenesis of T2DM. Interestingly, T2DM could also be a prominent reason for the mentioned epigenetic alterations.

CONCLUSION

This review article emphasized on the epigenetic modifications associated with T2DM and discussed the consequences in deterioration of the disease condition.

摘要

背景与目的

2型糖尿病(T2DM)是一种多因素代谢紊乱疾病。胰腺β细胞功能障碍和胰岛素抵抗是T2DM最常见且关键的发病环节。越来越多的证据表明,表观遗传修饰通过影响包括胰腺β细胞分化、发育以及维持正常β细胞功能等重要生物学过程的改变,与T2DM的发病机制相关。外周葡萄糖摄取组织的胰岛素敏感性也会因表观遗传机制的改变而发生变化。在本综述中,我们探讨了T2DM背景下主要的表观遗传改变及其对β细胞功能、胰岛素分泌和胰岛素抵抗的影响。

方法

我们研究了目前已知的与T2DM发病机制相关的表观遗传修饰,包括DNA甲基化、组蛋白翻译后修饰、ATP依赖的染色质重塑以及非编码RNA。在谷歌学术和PubMed上使用相关关键词搜索关于该主题的已发表文献,并对相关信息进行研究。

结果

表观遗传修饰引起基因表达的变化,而这些变化对于β细胞的正常发育和功能、胰岛素分泌及敏感性至关重要,进而导致T2DM的发病。有趣的是,T2DM也可能是上述表观遗传改变的一个重要原因。

结论

本文综述强调了与T2DM相关的表观遗传修饰,并讨论了其在疾病恶化过程中的影响。

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