Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance
文献类型：期刊论文
| 作者 | Luan, B; Zhao, J; Wu, HY; Duan, BY; Shu, GW; Wang, XY; Li, DS; Jia, WP; Kang, JH; Pei, G |
| 刊名 | NATURE
 |
| 出版日期 | 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 |
| 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. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。