Polarity Protein AF6 Controls Hepatic Glucose Homeostasis and Insulin Sensitivity by Modulating IRS1/AKT Insulin Pathway in an SHP2-Dependent Manner
文献类型：期刊论文
| 作者 | Dai, Cheng; Wang, Xinyu; Wu, Yanjun; Xu, Yi; Zhuo, Shu; Qi, Meiyan; Ji, Weiwei; Zhan, Lixing; , |
| 刊名 | DIABETES
 |
| 出版日期 | 2019 |
| 卷号 | 68期号:8页码:1577-1590 |
| ISSN号 | 0012-1797 |
| DOI | 10.2337/db18-0695 |
| 文献子类 | Article |
| 英文摘要 | Insulin resistance is a major contributing factor in the development of metabolic disease. Although numerous functions of the polarity protein AF6 (afadin and MLLT4) have been identified, a direct effect on insulin sensitivity has not been previously described. We show that AF6 is elevated in the liver tissues of dietary and genetic mouse models of diabetes. We generated liver-specific AF6 knockout mice and show that these animals exhibit enhanced insulin sensitivity and liver glycogen storage, whereas overexpression of AF6 in wild-type mice by adenovirus-expressing AF6 led to the opposite phenotype. Similar observations were obtained from in vitro studies. In addition, we discovered that AF6 directly regulates IRS1/AKT kinase-mediated insulin signaling through its interaction with Src homology 2 domain-containing phosphatase 2 (SHP2) and its regulation of SHP2's tyrosine phosphatase activity. Finally, we show that knockdown of hepatic AF6 ameliorates hyperglycemia and insulin resistance in high-fat diet-fed or db/db diabetic mice. These results demonstrate a novel function for hepatic AF6 in the regulation of insulin sensitivity, providing important insights about the metabolic role of AF6. |
| 学科主题 | Endocrinology & Metabolism |
| WOS关键词 | RECEPTOR SUBSTRATE-1 ; KINASE LEADS ; PDZ DOMAIN ; GLYCOGEN ; AFADIN ; LKB1 ; LIVER ; ACTIVATION ; BINDING ; AF-6 |
| 语种 | 英语 |
| WOS记录号 | WOS:000476794600005 |
| 出版者 | AMER DIABETES ASSOC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1303]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Key Lab Nutr Metab & Food Safety,Shanghai Ins, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Dai, Cheng,Wang, Xinyu,Wu, Yanjun,et al. Polarity Protein AF6 Controls Hepatic Glucose Homeostasis and Insulin Sensitivity by Modulating IRS1/AKT Insulin Pathway in an SHP2-Dependent Manner[J]. DIABETES,2019,68(8):1577-1590. |
| APA | Dai, Cheng.,Wang, Xinyu.,Wu, Yanjun.,Xu, Yi.,Zhuo, Shu.,...&,.(2019).Polarity Protein AF6 Controls Hepatic Glucose Homeostasis and Insulin Sensitivity by Modulating IRS1/AKT Insulin Pathway in an SHP2-Dependent Manner.DIABETES,68(8),1577-1590. |
| MLA | Dai, Cheng,et al."Polarity Protein AF6 Controls Hepatic Glucose Homeostasis and Insulin Sensitivity by Modulating IRS1/AKT Insulin Pathway in an SHP2-Dependent Manner".DIABETES 68.8(2019):1577-1590. |
入库方式： OAI收割
来源：上海营养与健康研究所
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