Ms-275, a class 1 histone deacetylase inhibitor augments glucagon-like peptide-1 receptor agonism to improve glycemic control and reduce obesity in diet-induced obese mice
Given its glycemic efficacy and ability to reduce the body weight, glucagon-like peptide 1 receptor (GLP-1R) agonism has emerged as a preferred treatment for diabetes associated with obesity. We here report that a small-molecule Class 1 histone deacetylase (HDAC) inhibitor Entinostat (MS-275) enhances GLP-1R agonism to potentiate glucose-stimulated insulin secretion and decrease body weight in diet-induced obese (DIO) mice. MS-275 is not an agonist or allosteric activator of GLP-1R but enhances the sustained receptor-mediated signaling through the modulation of the expression of proteins involved in the signaling pathway. MS-275 and liraglutide combined therapy improved fasting glycemia upon short-term treatment and a chronic administration causes a reduction of obesity in DIO mice. Overall, our results emphasize the therapeutic potential of MS-275 as an adjunct to GLP-1R therapy in the treatment of diabetes and obesity
Bele, Shilpak; Girada, Shravan Babu; Ray, Aramita; Gupta, Abhishek; Oruganti, Srinivas; Babu, Phanithi Prakash; Rayalla, Rahul S.R.; Kalivendi, Shashi Vardhan; Ibrahim, Ahamed; Puri, Vishwajeet; Adalla, Venkateswar; Katika, Madhumohan R.; Dimarchi, Richard; and Mitra, Prasenjit, "Ms-275, a class 1 histone deacetylase inhibitor augments glucagon-like peptide-1 receptor agonism to improve glycemic control and reduce obesity in diet-induced obese mice" (2020). Biomedical Sciences Open Access Publications. 189.