TSPA as a novel ATF6 alpha translocation inducer efficiently ameliorates insulin sensitivity restoration and glucose homeostasis in db/db mice

doi:10.1016/j.bbrc.2018.04.025

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	TSPA as a novel ATF6 alpha translocation inducer efficiently ameliorates insulin sensitivity restoration and glucose homeostasis in db/db mice
	Zhou, Tingting 4,5; Cheng, Yanhua 3; Yan, Wenzhong 2; Shi, Xiaofan 5; Xu, Xin 5; Zhou, Jinpei 3; Li, Jian 2; Chen, Jing5 ; Shen, Xu1,5
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2018-05-23
卷号	499 期号:4 页码:948-953
关键词	ATF6 alpha ER stress insulin resistance TSPA T2DM
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2018.04.025
文献子类	Article
英文摘要	Activating transcription factor 6 alpha (ATF6 alpha) as a transducer in unfolded protein response (UPR), plays an important role in liver glucose metabolism and insulin resistance. Thus, targeting ATF6 alpha activation has been proposed to be a potential strategy for anti-T2DM drug discovery. Here, we determined that small molecule 2-15-[1-(4-chlorophenoxy)ethyl]-4-pheny1-4H-1,2,4-triazol-3-yl]sulfanyl-N-(1,5-dimethy1-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide (TSPA) functioned as an ATF6 alpha translocation inducer effectively promoting ATF6 alpha translocation into nucleus and ameliorating glucose homeostasis on db/db mice. TSPA promoted ATF6 alpha translocation into nucleus without incresing C/EBP-homologous protein (CHOP) expression. TSPA restored the tunicamycin (TM)-stimulated insulin receptor (IR) desensitization through ATF6 alpha activation, inhibited gluconeogenesis and efficiently improved glucose homeostasis on db/db mice. Furthermore, TSPA protected insulin pathway involving p38/X-box binding protein 1s (Xbp1s)/ER chaperones signaling pathway. Our current study has determined that ATF6 alpha was a promising therapeutic target and also highlighted the potential of TSPA in the treatment of type 2 diabetes mellitus (T2DM). (C) 2018 Elsevier Inc. All rights reserved.
资助项目	National Natural Science Foundation of China[81473141] ; National Natural Science Foundation of China[81703806] ; NSFC-TRF collaboration projects[NSFC 81561148011] ; Fundamental Research Funds for the Central Universities[JUSRP11863]
WOS关键词	ENDOPLASMIC-RETICULUM STRESS ; ER STRESS ; TRANSCRIPTION FACTOR ; HEPATIC GLUCONEOGENESIS ; MOUSE MODEL ; ATF6 ; ACTIVATION ; MECHANISM ; PATHWAYS ; PROTECTS
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000431286300034
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279750]
专题	药物安全性评价中心
通讯作者	Li, Jian; Chen, Jing
作者单位	1.Nanjing Univ Chinese Med, Sch Med & Life Sci, State Key Lab Cultivat Base TCM Qual & Efficacy, 138 Xianlin Rd, Nanjing 210023, Jiangsu, Peoples R China 2.East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China; 3.China Pharmaceut Univ, Sch Pharm, Nanjing 210009, Jiangsu, Peoples R China; 4.Jiangnan Univ, Wuxi Sch Med, 1800 Lihu Rd, Wuxi 214122, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Zhou, Tingting,Cheng, Yanhua,Yan, Wenzhong,et al. TSPA as a novel ATF6 alpha translocation inducer efficiently ameliorates insulin sensitivity restoration and glucose homeostasis in db/db mice[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2018,499(4):948-953.
APA	Zhou, Tingting.,Cheng, Yanhua.,Yan, Wenzhong.,Shi, Xiaofan.,Xu, Xin.,...&Shen, Xu.(2018).TSPA as a novel ATF6 alpha translocation inducer efficiently ameliorates insulin sensitivity restoration and glucose homeostasis in db/db mice.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,499(4),948-953.
MLA	Zhou, Tingting,et al."TSPA as a novel ATF6 alpha translocation inducer efficiently ameliorates insulin sensitivity restoration and glucose homeostasis in db/db mice".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 499.4(2018):948-953.