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Quercetin differently regulates insulin‐mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes
Author(s) -
Xu Manli,
Hu Juanjuan,
Zhao Wenwen,
Gao Xuejiao,
Jiang Cuihua,
Liu Kang,
Liu Baolin,
Huang Fang
Publication year - 2014
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300510
Subject(s) - glut4 , glucose transporter , ampk , insulin , glucose uptake , insulin receptor , medicine , quercetin , endocrinology , phosphorylation , biology , insulin resistance , microbiology and biotechnology , chemistry , protein kinase a , biochemistry , antioxidant
Scope 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. Methods and 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. Conclusion 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.