title: Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes.
abstract: METHODS
  Quercetin is the most abundant dietary flavonol with beneficial regulation of glucose homeostasis, but its regulation of insulin action remains uncertain. This study aims to investigate the effects of quercetin on insulin-mediated glucose transporter 4 (GLUT4) translocation under basal and inflammatory conditions as well as the molecular mechanisms in adipocytes.
  
  
  RESULTS
  The effects of quercetin on insulin-mediated GLUT4 translocation in 3T3-L1 cells under basal and insulin resistant conditions were investigated. Meanwhile, we investigated the effect of quercetin on AMP-activated protein kinase (AMPK) activation implicated in regulation of insulin action. Quercetin inhibited insulin-mediated GLUT4 translocation by inhibiting AS160 phosphorylation. Differently, when inflammatory challenge impaired insulin action in 3T3-L1 cells, quercetin inhibited IκB kinase β (IKKβ) phosphorylation and facilitated insulin signaling, leading to the restoration of insulin-mediated AS160 phosphorylation and downstream GLUT4 translocation. AMPK inhibitor Compound C or knockdown of AMPKα by small interfering RNA (siRNA) abolished both actions of quercetin. Results from mice adipose tissue (AT) further confirmed its positive regulation of AMPK phosphorylation and opposite effects on AS160 phosphorylation in vivo.
  
  
  CONCLUSIONS
  Quercetin demonstrated divergent effects on insulin-mediated GLUT4 translocation in adipocytes under basal and insulin resistant conditions, which were related to its regulation of AMPK activity.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Manli
authors.initials: M
authors.lastname: Xu
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Hu
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhao
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Gao
authors.forename: Cuihua
authors.initials: C
authors.lastname: Jiang
authors.forename: Kang
authors.initials: K
authors.lastname: Liu
authors.forename: Baolin
authors.initials: B
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D034741:RNA, Small Interfering; C495693:Slc2a4 protein, mouse; C505647:Tbc1d4 protein, mouse; D009569:Nitric Oxide; D011794:Quercetin; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D055372:AMP-Activated Protein Kinases
keywords: Adenosine 5′-monophosphate-activated protein kinase; Adipocytes; Akt substrate of 160 kDa; Insulin resistance; Quercetin