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Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor  期刊论文  

  • 编号:
    1d869a4b-d0bb-41e2-aef7-ae974f78489e
  • 作者:
    Wang, Xuan(王璇)[1,2,3]Wang, Meichen[1,2];Li, Hongmin[4];Lan, Xi[1,2];Liu, Li[1,2];Li, Jiaxi[1,2];Li, Yue[1,2];Li, Jing[1,2];Yi, Jing[1,2];Du, Xiaojuan[1,2];Yan, Jidong[1,2];Han, Yan[1,2];Zhang, Fujun[1,2];Liu, Min[5];Lu, Shemin[1,2];Li, Dongmin[1,2];
  • 语种:
    English
  • 期刊:
    MOLECULAR AND CELLULAR ENDOCRINOLOGY ISSN:0303-7207 2015 年 416 卷 C 期 (57 - 69) ; NOV 15
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  • 关键词:
  • 摘要:

    Objective: The study aims to find regulatory microRNA(s) responsible for Clown-regulated insulin receptor (InsR) in the liver of HFD-MetS E3 rats with insulin resistance. Methods: Firstly, hepatic insulin resistance in HFD-MetS E3 rats was evaluated by RT-qPCR, western blotting, immunohistochemistry and PAS staining. Secondly, the candidate miRNAs targeting rat InsR were predicted through online softwares and detected in the liver of HFD-MetS E3 rats with insulin resistance. Then, the expression of InsR, phosphorylated IRS-1 (pIRS-1) at Tyr632, phosphorylated Alas (pAKTs) at Ser473 and Thr308, phosphorylated GSK-3 beta (p GSK-3 beta) at Ser9, phosphorylated GS (pGS) at Ser641 and the glycogen content were detected in CBRH-7919 cells treated with 100 nM insulin for different time periods by western blotting or PAS staining respectively, after transient transfection with miR-497 mimics or inhibitors for 24 h. Lastly, the relation between miR-497 and InsR was further determined using dual luciferase reporter assay. Results: Elevated miR-497 was negatively related with down-regulated InsR in the liver of HFD-MetS E3 rats with insulin resistance. Comparing with the mNC group, glycogen content and the expression of InsR, pIRS-1 (Tyr632), pAKTs (Ser473 and Thr308) and pGSK-3 beta (Ser9) decreased significantly in CBRH-7919 cells, while pGS (Ser641) increased significantly, after transient transfection with miR-497 mimics for 24 h and treatment with 100 nM insulin for corresponding time periods, counter to those results in CBRH-7919 cells after similar procedures with miR-497 inhibitors and insulin. In addition, dual luciferase reporter assay further confirmed that miR-497 can bind to the 3'UTR of rat InsR. Conclusion: Insulin receptor is the target gene of miR-497, and elevated miR-497 might induce hepatic insulin resistance in HFD-MetS E3 Rats through inhibiting the expression of insulin receptor and confining the activation of IRS-1/PI3K/Akt/GSK-3 beta/GS pathway to insulin. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

  • 推荐引用方式
    GB/T 7714:
    Wang Xuan,Wang Meichen,Li Hongmin, et al. Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor [J].MOLECULAR AND CELLULAR ENDOCRINOLOGY,2015,416(C):57-69.
  • APA:
    Wang Xuan,Wang Meichen,Li Hongmin,Lan Xi,&Li Dongmin.(2015).Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor .MOLECULAR AND CELLULAR ENDOCRINOLOGY,416(C):57-69.
  • MLA:
    Wang Xuan, et al. "Upregulation of miR-497 induces hepatic insulin resistance in E3 rats with HFD-MetS by targeting insulin receptor" .MOLECULAR AND CELLULAR ENDOCRINOLOGY 416,C(2015):57-69.
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