Histone deacetylases and their inhibitors: molecular mechanisms and therapeutic implications in diabetes mellitus

Epigenetic mechanisms such as DNA methylation, histone modification and microRNA changes have been shown to be important for the regulation of cellular functions. Among them, histone deacetylases (HDACs) are enzymes that balance the acetylation activities of histone acetyltransferases in chromatin remodeling and play essential roles in gene transcription to regulate cell proliferation, migration and death. Recent studies indicate that HDACs are promising drug targets for a wide range of diseases including cancer, neurodegenerative and psychiatric disorders, cardiovascular dysfunction, autoimmunity and diabetes mellitus. This review highlights the role of HDACs in diabetes mellitus and outlines several important cellular and molecular mechanisms by which HDACs regulate glucose homeostasis and can be targeted for the treatment of diabetic microvascular complications. It is hoped that our understanding of the role of HDACs in diabetes mellitus will lead to the development of better diagnostic tools and the design of more potent and specific drugs targeting selective HDAC proteins for the treatment of the disease.

Graphical abstractThis review highlights the role of HDACs in diabetes mellitus and outlines several important cellular and molecular mechanisms by which HDACs regulate glucose homeostasis and can be targeted for the treatment of diabetic microvascular complications.Figure optionsDownload full-size imageDownload as PowerPoint slide