title: MiR-301a mediates the effect of IL-6 on the AKT/GSK pathway and hepatic glycogenesis by regulating PTEN expression.
abstract: OBJECTIVE
  IL-6 has been implicated in the pathogenesis of insulin resistance. MiR-301a plays an important role in various biological and pathological processes, including cellular development and differentiation, inflammation, apoptosis and cancer. However, whether miR-301a mediates IL-6-induced insulin resistance in hepatocytes remains unknown.
  
  
  METHODS
  The activation of AKT/GSK pathway and the level of glycogenesis were examed in NCTC 1469 cells transfected miR-301a mimics and inhibitor. Using computational miRNA target prediction database, PTEN was a target of miR-301a. The effect of miR-301a on PTEN expression was evaluated using Luciferase assay and western blot. A PTEN-specific siRNA was used to further determine the effect of PTEN on IL-6-induced insulin resistance.
  
  
  RESULTS
  In vivo and in vitro treatment with IL-6 was led to down-regulation of miR-301a, accompanied by impairment of theAKT/GSK pathway and glycogenesis. Importantly, over-expression of miR-301a rescued IL-6-induced decreased activation of the AKT/GSK pathway and hepatic glycogenesis. In contrast, down-regulation of miR-301a induced impaired phosphorylation of AKT and GSK, accompanied by reduced glycogenesis in hepatocytes. Moreover, our results indicate that suppression of PTEN, a target of miR-301a, diminished the effect of IL-6 on the AKT/GSK pathway and hepatic glycogenesis.
  
  
  CONCLUSIONS
  We present novel evidence of the contribution of miR-301a to IL-6-induced insulin resistance by direct regulation of PTEN expression.
authors: Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.
authors: Lin
authors: L
authors: Dou
authors: Shuyue
authors: S
authors: Wang
authors: Xiaofang
authors: X
authors: Sui
authors: Xiangyu
authors: X
authors: Meng
authors: Tao
authors: T
authors: Shen
authors: Xiuqing
authors: X
authors: Huang
authors: Jun
authors: J
authors: Guo
authors: Weiwei
authors: W
authors: Fang
authors: Yong
authors: Y
authors: Man
authors: Jianzhong
authors: J
authors: Xi
authors: Jian
authors: J
authors: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D050261:Glycogenolysis / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015850:Interleukin-6; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D006003:Glycogen; D038341:Glycogen Synthase Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse