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

doi:10.7554/ELIFE.52212

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 journal › Article › peer-review

11 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 language	English (US)
Article number	e52212
Pages (from-to)	1-33
Number of pages	33
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/ELIFE.52212
State	Published - Dec 2020
Externally published	Yes

ASJC Scopus subject areas

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

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10.7554/ELIFE.52212

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Bele, S., Girada, S. B., Ray, A., Gupta, A., Oruganti, S., Babu, P. P., Rayalla, R. S. R., Kalivendi, S. V., Ibrahim, A., Puri, V., Adalla, V., Katika, M. R., Dimarchi, R., & Mitra, P. (2020). 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. eLife, 9, 1-33. Article e52212. https://doi.org/10.7554/ELIFE.52212

Bele, S, Girada, SB, Ray, A, Gupta, A, Oruganti, S, Babu, PP, Rayalla, RSR, Kalivendi, SV, Ibrahim, A, Puri, V, Adalla, V, Katika, MR, Dimarchi, R & Mitra, P 2020, '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', eLife, vol. 9, e52212, pp. 1-33. https://doi.org/10.7554/ELIFE.52212

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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.",

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AU - Ibrahim, Ahamed

AU - Puri, Vishwajeet

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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

Abstract

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