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.
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.
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MS-275，一种1类组蛋白去乙酰化酶抑制剂，增强胰高血糖素样肽-1受体激动作用，以改善饮食诱导的肥胖小鼠的血糖控制并减少肥胖。
DOI：
10.7554/elife.52212
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发表时间：
2020-12-22
期刊：
影响因子：
7.7
通讯作者：
Mitra P
中科院分区：
文献类型：
--
作者：
Bele S;Girada SB;Ray A;Gupta A;Oruganti S;Prakash Babu P;Rayalla RS;Kalivendi SV;Ibrahim A;Puri V;Adalla V;Katika MR;DiMarchi R;Mitra P
鉴于其血糖功效和减轻体重的能力，胰高血糖素样肽1受体（GLP-1 R）激动剂已成为与肥胖相关的糖尿病的优选治疗。我们在此报告了一种小分子1类组蛋白脱乙酰酶（HDAC）抑制剂恩替司他（MS-275）增强GLP-1 R激动作用，以增强葡萄糖刺激的胰岛素分泌并降低饮食诱导肥胖（DIO）小鼠的体重。MS-275不是GLP-1 R的激动剂或变构激活剂，但可通过调节参与信号传导途径的蛋白质表达来增强持续的受体介导的信号传导。MS-275和利拉鲁肽联合治疗在短期治疗后改善了空腹血糖，长期给药导致DIO小鼠肥胖减少。总体而言，我们的结果强调了MS-275作为GLP-1 R治疗的辅助治疗在糖尿病和肥胖症治疗中的治疗潜力。
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.
人胰岛素基因座中的染色质结构，表观遗传机理和远距离相互作用。
DOI：
10.1111/j.1463-1326.2012.01645.x
发表时间：
2012-10
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Xu Z;Lefevre GM;Felsenfeld G
通讯作者：
Felsenfeld G
将脂肪酸应激与β细胞线粒体动力学联系起来。
影响因子：
7.7
作者：
Wiederkehr A;Wollheim CB
通讯作者：
Wollheim CB