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1型糖尿病的新型治疗方法。

Novel methods of type 1 diabetes treatment.

作者信息

Jayaraman Sundararajan

机构信息

Department of Surgery, University of Illinois at Chicago, 909 S. Wolcott Ave., COMRB 8143, Chicago, IL 60612, USA.

出版信息

Discov Med. 2014 Jun;17(96):347-55.

Abstract

Type 1 diabetes is an autoimmune disease characterized by the cell-mediated destruction of insulin-producing β-cells, leading to impaired glucose homeostasis, insulin insufficiency, and other complications. Although classic genetic studies have linked numerous genes to the susceptibility of developing diabetes, the mechanisms by which they influence the disease course remain poorly understood. Epigenetics, inheritable changes in gene expression that occur without accompanying genetic mutation, can both serve as a link between the environment and genetic causes of disease and help explain some of the observed vagaries of diabetes. Elucidation of the epigenetic landscape as it relates to putative treatment modalities is highly warranted. Drugs with histone deacetylase activity are in clinical trials for cancer and certain inflammatory diseases with high safety profiles and they hold similar promise for amelioration of type 1 diabetes with diminished secondary complications. Full-fledged studies on the epigenetics of type 1 diabetes are highly likely to provide novel tools for the manipulation of the disease in the years to come. In this review, epigenetic regulation mediated by small molecular inhibitors of histone deacetylases and their potential for preventing diabetes are discussed. Insights into the nature of the genetic mechanisms unraveled by these studies are also highlighted.

摘要

1型糖尿病是一种自身免疫性疾病,其特征是细胞介导的胰岛素生成β细胞破坏,导致葡萄糖稳态受损、胰岛素不足及其他并发症。尽管经典遗传学研究已将众多基因与患糖尿病的易感性联系起来,但它们影响疾病进程的机制仍知之甚少。表观遗传学是指在不伴随基因突变的情况下发生的基因表达可遗传变化,它既可以作为疾病环境因素与遗传因素之间的联系,也有助于解释1型糖尿病中一些观察到的变幻莫测的现象。阐明与假定治疗方式相关的表观遗传格局非常必要。具有组蛋白脱乙酰酶活性的药物正在针对癌症和某些炎症性疾病进行临床试验,安全性良好,它们在改善1型糖尿病并减少继发性并发症方面也有类似前景。全面研究1型糖尿病的表观遗传学极有可能在未来几年为控制该疾病提供新工具。在这篇综述中,将讨论由组蛋白脱乙酰酶小分子抑制剂介导的表观遗传调控及其预防糖尿病的潜力。还将强调这些研究揭示的遗传机制的本质。

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