Potential role of histone deacetylase 3 specific inhibitor Compound A in diabetes treatment
Potential role of histone deacetylase 3 specific inhibitor Compound A in diabetes treatment作者机构：The State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College
出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)
年 卷 期：2019年第10期
页 面：758-758页
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：CAMS Innovation Fund for Medical Sciences(2016-I2M-4-001 2017-I2M-1-010) Drug Innovation Major Project(2018ZX09711001-003-005) National Natural Science Foundation of China(81603027)
主 题：histone deacetylase diabetes β cell insulin
摘 要：OBJECTIVE In order to develop histone deacetylase 3(HDAC3) as a therapeutic target of diabetes,this project was mainly to study the antidiabetic potential role of HDAC3 specific inhibitor and its *** HDAC3-selective inhibition small molecule Compound A was found through screening method in *** vivo, the potency of Compound A on regulating blood glucose was test in streptozotocin(STZ) and high fat diet(HFD) induced diabetic mice, and hyperglycemic clamp technique was used to evaluate its effect on β cell function. At the same time, the ability of Compound A to promote insulin secretion was also assessed in β cells. RESULTS Compound A could down-regulate the fasting glycemia and ameliorate the oral glucose tolerance significantly. It could also augment the glucose infusion rate, and improve phaseⅠinsulin secretionand β cel function during the hyperglycemic clamp test. Besides, Compound A could promote insulin secretion in β cell line MIN6 cells, and up-regulate the expression level of Ins1 and Ins2. CONCLUSION HDAC3 specific inhibitor Compound A had the antidiabetic effect in STZ/HFD induced diabetic mice, which could be related to amelioration of β cell function. Furthermore,HDAC3 might be a novel drug target for diabetes treatment.
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