title: MiR-26b modulates insulin sensitivity in adipocytes by interrupting the PTEN/PI3K/AKT pathway.
abstract: BACKGROUND
  MicroRNAs (miRNAs) have emerged as epigenetic regulators of metabolism and energy homeostasis. There is a growing body of evidence pointing to miRNAs that have important regulatory roles in insulin sensitivity.
  
  
  OBJECTIVE
  The aim of this work was to explore the expression and mechanism of action of miR-26b in obesity-related insulin resistance (IR) in adipocytes.
  
  
  METHODS
  Quantitative real-time PCR was performed to determine miR-26b expression in obese rodent models, human obesity subjects and insulin-resistant adipocytes. We analysed the roles of miR-26b overexpression and inhibition on glucose uptake in adipocytes. Western blotting was used to detect the levels of protein molecules involved in the phosphoinositide-3-kinase (PI3K) pathway. Bioinformatics and the Dual Luciferase Assay were used to identify the target gene of miR-26b. We assessed the regulatory roles of miR-26b on the phosphatase and tensin homologue (PTEN)/PI3K/AKT pathway and the relationship between miR-26b and the metabolism of human obese subjects.
  
  
  RESULTS
  Levels of miR-26b are reduced in visceral adipose tissue (VAT) in obese rodent models, human obesity and insulin-resistant adipocytes. MiR-26b promotes insulin-stimulated glucose uptake and increases insulin-stimulated glucose transporter type 4 translocation to the plasma membrane in human mature adipocytes. MiR-26b modulates insulin-stimulated AKT activation via inhibition of its target gene, PTEN, and significantly increases insulin sensitivity via the PTEN/PI3K/AKT pathway. The expression level of miR-26b negatively correlates with increasing body mass index and homeostasis model assessment for IR in human obese subjects.
  
  
  CONCLUSIONS
  Decreased miR-26b expression in VAT may be involved in obesity-related IR by interrupting the PTEN/PI3K/AKT pathway.
authors.affiliation: Department of Clinical Laboratory, The 82nd Hospital of the People's Liberation Army, Huaian, China.
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: C
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: G
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, The 82nd Hospital of the People's Liberation Army, Huaian, China.
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: C
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Clinical Laboratory, The 82nd Hospital of the People's Liberation Army, Huaian, China.
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.affiliation: Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: F
authors.initials: F
authors.lastname: Huang
authors.affiliation: Institute of Pediatrics, Nanjing Medical University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Clinical Laboratory, The 82nd Hospital of the People's Liberation Army, Huaian, China.
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, The 82nd Hospital of the People's Liberation Army, Huaian, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D046228:Microarray Analysis; D009765:Obesity / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C556274:MIRN26 microRNA, rat; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C487216:Pten protein, rat