摘要
背景:SIRTUIN1是组蛋白和非组蛋白脱乙酰作用的表观遗传酶。 它主要作用于代谢传感器,该传感器响应于通过脱乙酰基来改变能量状态。非常关键的转录因子和辅助因子。通过这种方式,Sirtuin 1可以调节线粒体功能和生物发生、氧化应激、炎症、凋亡和细胞衰老。干扰所有这些现象都促进了糖尿病并发症的发病。这些疾病与慢性高血糖有着不可分割的联系,而高血糖具有很强的表观遗传决定因素。 目的:总结Sirtuin 1在糖尿病并发症发生、发展和治疗中的作用。 方法:我们查阅了大量文献,描述了Sirtuin 1在病理生理和治疗各种糖尿病并发症方面的重要性,直到2017。我们关注的是这个例子S合成和天然化合物-介导的Sirtuin 1上调与Sirtuin 1相关的表观遗传学。 结果:Sirtuin 1的减少与内皮功能障碍和代谢记忆有关,是微血管和大血管并发症发生的基础。谢绝Sirtuin 1也参加糖尿病睾丸和勃起功能障碍。Sirtuin 1通过天然存在的抗氧化剂和抗炎物质如白藜芦醇、反式δ-viniferin、维生素D等而升高。西轻微的,Sirtuin 1水平在治疗后会增加标准的高血糖(二甲双胍,exenatide,liraglutide),降压(沙坦),降脂(纤维蛋白,他汀类)和抗凝血剂。药物。在表观遗传学方面,许多miRNAs触发Sirtuin 1的减少,这进一步促进了Sirtuin 1的组蛋白乙酰化--这与糖尿病基因有关。 结论:有证据表明,Sirtuin 1上调可能是治疗糖尿病并发症发展和进展的有效方法。
关键词: SIRT 1,胰岛素抵抗,糖尿病,糖尿病并发症,SIRT 1相关表观遗传学,SIRT 1靶向药物。
Current Medicinal Chemistry
Title:SIRT1 as a Therapeutic Target in Diabetic Complications
Volume: 25 Issue: 9
关键词: SIRT 1,胰岛素抵抗,糖尿病,糖尿病并发症,SIRT 1相关表观遗传学,SIRT 1靶向药物。
摘要: Background: Sirtuin1 is an epigenetic enzyme involved in histone and nonhistone protein deacetylation. It acts primarily as a metabolic sensor, which responses to changing energy status by deacetylating crucial transcription factors and cofactors. In this way, Sirtuin1 regulates mitochondrial function and biogenesis, oxidative stress, inflammation, apoptosis and cellular senescence. Disturbance of all of these phenomena promotes the pathogenesis of diabetic complications. These disorders are inseparably connected with chronic hyperglycemia, which possesses a strong epigenetic determinant.
Objective: To summarize the contemporary knowledge regarding the role of Sirtuin1 in the development, progression and therapy of diabetic complications.
Methods: We extensively searched literature describing the importance of Sirtuin1 in pathophysiology and treatment of all kinds of diabetic complications till September 2017. We focused on the examples of synthetic and natural compounds-mediated Sirtuin1 upregulation along with Sirtuin1-associated epigenetics.
Results: Reduction of Sirtuin1 is implicated in endothelial dysfunction and metabolic memory, underlying the development of micro- and macrovascular complications. Declined Sirtuin1 also participates in diabetic testicular and erectile dysfunction. Sirtuin1 is elevated by naturally occurring anti-oxidant and anti-inflammatory compounds such as resveratrol, trans-δ-viniferin, vitamin D and more. Similarly, Sirtuin1 level increases after treatment with standard antihyperglycemic (metformin, exenatide, liraglutide), antihypertensive (sartans), lipid-lowering (fibrates, statins) and anticoagulant (fidarestat) drugs. Regarding epigenetics, a number of miRNAs trigger Sirtuin1 decrease, which further contributes to histone acetylation of Sirtuin1-regulated and relevant for diabetes genes.
Conclusion: Evidence strongly suggest that Sirtuin1 upregulation may serve as a potent therapeutic approach against development and progression of diabetic complications.
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Cite this article as:
SIRT1 as a Therapeutic Target in Diabetic Complications, Current Medicinal Chemistry 2018; 25 (9) . https://dx.doi.org/10.2174/0929867324666171107103114
DOI https://dx.doi.org/10.2174/0929867324666171107103114 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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