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组蛋白去乙酰化酶(HDAC)抑制作为治疗糖尿病的新方法。

Histone deacetylase (HDAC) inhibition as a novel treatment for diabetes mellitus.

机构信息

Center for Medical Research Methodology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Mol Med. 2011 May-Jun;17(5-6):378-90. doi: 10.2119/molmed.2011.00021. Epub 2011 Jan 25.

Abstract

Both common forms of diabetes have an inflammatory pathogenesis in which immune and metabolic factors converge on interleukin-1β as a key mediator of insulin resistance and β-cell failure. In addition to improving insulin resistance and preventing β-cell inflammatory damage, there is evidence of genetic association between diabetes and histone deacetylases (HDACs); and HDAC inhibitors (HDACi) promote β-cell development, proliferation, differentiation and function and positively affect late diabetic microvascular complications. Here we review this evidence and propose that there is a strong rationale for preclinical studies and clinical trials with the aim of testing the utility of HDACi as a novel therapy for diabetes.

摘要

两种常见形式的糖尿病都具有炎症发病机制,其中免疫和代谢因素集中在白细胞介素-1β上,作为胰岛素抵抗和β细胞衰竭的关键介质。除了改善胰岛素抵抗和预防β细胞炎症损伤外,还有证据表明糖尿病与组蛋白去乙酰化酶(HDAC)之间存在遗传关联;并且 HDAC 抑制剂(HDACi)可促进β细胞的发育、增殖、分化和功能,并对糖尿病的晚期微血管并发症产生积极影响。在这里,我们回顾了这方面的证据,并提出了一个强有力的理由,即需要进行临床前研究和临床试验,以测试 HDACi 作为治疗糖尿病的新疗法的效用。

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