Lawless M W, O'Byrne K J, Gray S G
Centre for Liver Disease, School of Medicine and Medical Science, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
Curr Diabetes Rev. 2009 Aug;5(3):201-9. doi: 10.2174/157339909788920956.
Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the "histone code" describes the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as "chemical chaperones" to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes.
在全球范围内，肥胖和糖尿病（尤其是2型糖尿病）是对世界健康的重大挑战。尽管经过了数十年的深入研究，但糖尿病发病机制及与肥胖相关状况所涉及的遗传基础仍知之甚少。最近的进展带来了令人兴奋的新发展，表明表观遗传学是支撑糖尿病和肥胖相关疾病的重要机制。一种被称为“组蛋白密码”的表观遗传机制描述了这样一种观点，即组蛋白翻译后修饰的特定模式就像一种分子“密码”，被非组蛋白蛋白质识别并用于调节特定的染色质功能。其中受到显著关注的一种修饰是组蛋白乙酰化。调节这种修饰的酶被称为赖氨酸乙酰转移酶（KATs）和组蛋白脱乙酰酶（HDACs）。由于其保守的催化结构域，HDACs一直是积极的治疗靶点。一些已知的HDAC抑制剂（HDACi）也已被证明可作为“化学伴侣”来缓解糖尿病症状。在本综述中，我们讨论了有关HDACs在调节伴侣功能中的作用的现有证据，以及这可能如何对糖尿病的管理产生影响。
