(+)-Rutamarin as a Dual Inducer of Both GLUT4 Translocation and Expression Efficiently Ameliorates Glucose Homeostasis in Insulin-Resistant Mice

doi:10.1371/journal.pone.0031811

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	(+)-Rutamarin as a Dual Inducer of Both GLUT4 Translocation and Expression Efficiently Ameliorates Glucose Homeostasis in Insulin-Resistant Mice
	Zhang, Yu 1; Zhang, Haitao 1; Yao, Xin-gang 1; Shen, Hong 1; Chen, Jing1 ; Li, Chenjing 1; Chen, Lili1 ; Zheng, Mingyue1 ; Ye, Jiming 2; Hu, Lihong 1
刊名	PLOS ONE
	2012-02-27
卷号	7 期号:2
ISSN号	1932-6203
DOI	10.1371/journal.pone.0031811
文献子类	Article
英文摘要	Glucose transporter 4 (GLUT4) is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM). Therefore, induction of GLUT4 translocation or/and expression is a promising strategy for anti-T2DM drug discovery. Here we report that the natural product (+)-Rutamarin (Rut) functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced obese (DIO) mice based assays further confirm the Rut-induced improvement of glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B) inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor alpha (RXR alpha), Rut potently increases GLUT4 expression. Furthermore, by using molecular modeling and crystallographic approaches, the possible binding modes of Rut to these two targets have been also determined at atomic levels. All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.
资助项目	State Key Program of Basic Research of China[2010CB912501] ; State Key Program of Basic Research of China[2009CB918502] ; National Natural Science Foundation of China[90713046] ; National Natural Science Foundation of China[30890044] ; National Natural Science Foundation of China[10979072] ; Science Foundation of Shanghai[11XD1406100] ; Science Foundation of Shanghai[11ZR1444500] ; Foundation of Chinese Academy of Sciences[KSCX2-EW-Q-3]
WOS关键词	PROTEIN-TYROSINE PHOSPHATASES ; ACTIVATED RECEPTOR-GAMMA ; PPAR-GAMMA ; METABOLIC SYNDROME ; TRANSPORTER GLUT4 ; MUSCLE-CELLS ; 3T3-L1 ADIPOCYTES ; SKELETAL-MUSCLE ; RETINOIC ACID ; MECHANISM
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000302918500039
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278180]
专题	上海中药现代化研究中心中科院受体结构与功能重点实验室新药研究国家重点实验室药物发现与设计中心药物化学研究室药理学第三研究室
通讯作者	Zhang, Yu
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 2.RMIT Univ, Sch Hlth Sci, Melbourne, Vic, Australia
推荐引用方式 GB/T 7714	Zhang, Yu,Zhang, Haitao,Yao, Xin-gang,et al. (+)-Rutamarin as a Dual Inducer of Both GLUT4 Translocation and Expression Efficiently Ameliorates Glucose Homeostasis in Insulin-Resistant Mice[J]. PLOS ONE,2012,7(2).
APA	Zhang, Yu.,Zhang, Haitao.,Yao, Xin-gang.,Shen, Hong.,Chen, Jing.,...&Jiang, Hualiang.(2012).(+)-Rutamarin as a Dual Inducer of Both GLUT4 Translocation and Expression Efficiently Ameliorates Glucose Homeostasis in Insulin-Resistant Mice.PLOS ONE,7(2).
MLA	Zhang, Yu,et al."(+)-Rutamarin as a Dual Inducer of Both GLUT4 Translocation and Expression Efficiently Ameliorates Glucose Homeostasis in Insulin-Resistant Mice".PLOS ONE 7.2(2012).