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

Shilpak Bele, Shravan Babu Girada, Aramita Ray, Abhishek Gupta, Srinivas Oruganti, Phanithi Prakash Babu, Rahul S.R. Rayalla, Shashi Vardhan Kalivendi, Ahamed Ibrahim, Vishwajeet Puri, Venkateswar Adalla, Madhumohan R. Katika, Richard Dimarchi, Prasenjit Mitra

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere52212
Pages (from-to)1-33
Number of pages33
JournaleLife
Volume9
DOIs
StatePublished - Dec 2020
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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