Histone deacetylase inhibitors as antidiabetic agents: Advances and opportunities

• Published in: European journal of pharmacology 2022-11, Vol.935, p.175328-175328, Article 175328
• Main Authors: Sonthalia, Manisha, Roy, Bhramar Sinha, Chandrawanshi, Divya, Ganesh, Goutham V., Jayasuriya, Ravichandran, Mohandas, Sundhar, Rajagopal, Senthilkumar, Ramkumar, Kunka Mohanram
• Format: Article
• Language: English
• Subjects: Diabetes; HDAC inhibitors; HDACs; Insulin resistance; β-cell apoptosis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2022.175328

The loss of function or dysfunction of β-cells in the pancreas, attributed to the development of diabetes, involve alterations in genetic and epigenetic signatures. Recent evidences highlight the pathophysiological role of histone deacetylases (HDACs) in type 1 and type 2 diabetes. Indeed, most HDAC members have been linked to critical pathogenic events in diabetes, including redox imbalance, endoplasmic reticulum (ER) homeostasis perturbation, onset of oxidative stress and inflammation, which ultimately deteriorate β-cell function. Accumulating evidence highlights the inhibition of HDACs as a prospective therapeutic strategy. Several chemically synthesized small molecules have been investigated for their specific ability to inhibit HDACs (reffered as HDAC inibitors) in various experimental studies. This review provides insights into the critical pathways involved in regulating different classes of HDACs. Further, the intricate signaling networks between HDACs and the stress mediators in diabetes are also explored. We exhaustively sum up the inferences from various investigations on the efficiency of HDAC inhibitors in managing diabetes and its associated complications. [Display omitted]