糖尿病是一种损害新陈代谢的慢性疾病,其患病率已达到全球流行比例。大多数受影响的人患有2型糖尿病(T2DM),这是由胰腺内分泌胰岛细胞的数量或功能下降引起的,特别是β-细胞释放足够量的胰岛素以克服代谢组织的任何胰岛素抗性。遗传和表观遗传因素是T2DM的主要贡献者。表观遗传修饰剂,组蛋白脱乙酰酶(HDAC),是从组蛋白中去除乙酰基的酶,在各种分子过程中发挥重要作用,包括胰腺细胞的命运,胰岛素释放,胰岛素生产,胰岛素信号,和葡萄糖代谢。HDAC还管理与糖尿病相关的其他监管过程,如氧化应激,炎症,凋亡,和纤维化,通过网络和功能分析揭示。这篇综述解释了目前对HDAC在糖尿病病理生理学中的功能的理解。各种HDAC抑制剂(HDACi)的抑制作用,以及它们作为T2DM生物标志物和可能的治疗靶点的功能重要性。虽然它们在T2DM中的作用仍在显现,更好地了解HDACi的作用可能与改善胰岛素敏感性有关,保护β细胞并减少T2DM相关并发症,在其他人中。
Diabetes mellitus is a chronic disease that impairs metabolism, and its prevalence has reached an epidemic proportion globally. Most people affected are with type 2 diabetes mellitus (T2DM), which is caused by a decline in the numbers or functioning of pancreatic endocrine islet cells, specifically the β-cells that release insulin in sufficient quantity to overcome any insulin resistance of the metabolic tissues. Genetic and epigenetic factors have been implicated as the main contributors to the T2DM. Epigenetic modifiers, histone deacetylases (
HDACs), are enzymes that remove acetyl groups from histones and play an important role in a variety of molecular processes, including pancreatic cell destiny, insulin release, insulin production, insulin signalling, and glucose metabolism.
HDACs also govern other regulatory processes related to diabetes, such as oxidative stress, inflammation, apoptosis, and fibrosis, revealed by network and functional analysis. This review explains the current understanding of the function of
HDACs in diabetic pathophysiology, the inhibitory role of various HDAC inhibitors (HDACi), and their functional importance as biomarkers and possible therapeutic targets for T2DM. While their role in T2DM is still emerging, a better understanding of the role of HDACi may be relevant in improving insulin sensitivity, protecting β-cells and reducing T2DM-associated complications, among others.