Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance

	Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance
	Luan, B; Zhao, J; Wu, HY; Duan, BY; Shu, GW; Wang, XY; Li, DS; Jia, WP; Kang, JH; Pei, G
刊名	NATURE
	2009
卷号	457 期号:7233 页码:1146-U105
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,gpei@sibs.ac.cn
英文摘要	Insulin resistance, a hallmark of type 2 diabetes, is a defect of insulin in stimulating insulin receptor signalling(1,2), which has become one of the most serious public health threats. Upon stimulation by insulin, insulin receptor recruits and phosphorylates insulin receptor substrate proteins(3), leading to activation of the phosphatidylinositol-3-OH kinase (PI(3) K)-Akt pathway. Activated Akt phosphorylates downstream kinases and transcription factors, thus mediating most of the metabolic actions of insulin(4-6). beta-arrestins mediate biological functions of G-protein-coupled receptors by linking activated receptors with distinct sets of accessory and effecter proteins, thereby determining the specificity, efficiency and capacity of signals(7-11). Here we show that in diabetic mouse models, beta-arrestin-2 is severely downregulated. Knockdown of beta-arrestin-2 exacerbates insulin resistance, whereas administration of beta-arrestin-2 restores insulin sensitivity in mice. Further investigation reveals that insulin stimulates the formation of a new beta-arrestin-2 signal complex, in which beta-arrestin-2 scaffolds Akt and Src to insulin receptor. Loss or dysfunction of beta-arrestin-2 results in deficiency of this signal complex and disturbance of insulin signalling in vivo, thereby contributing to the development of insulin resistance and progression of type 2 diabetes. Our findings provide new insight into the molecular pathogenesis of insulin resistance, and implicate new preventive and therapeutic strategies against insulin resistance and type 2 diabetes.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	PHOSPHATIDYLINOSITOL 3-KINASE ; ACTIVATION ; PROTEIN ; KINASE ; AKT ; SRC ; OBESITY ; PHOSPHORYLATION ; TRANSDUCTION ; PATHWAYS
收录类别	SCI
语种	英语
WOS记录号	WOS:000263680100044
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1303]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Luan, B,Zhao, J,Wu, HY,et al. Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance[J]. NATURE,2009,457(7233):1146-U105.
APA	Luan, B.,Zhao, J.,Wu, HY.,Duan, BY.,Shu, GW.,...&Pei, G.(2009).Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance.NATURE,457(7233),1146-U105.
MLA	Luan, B,et al."Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance".NATURE 457.7233(2009):1146-U105.