Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes

被引:37
作者
Xu, Manli [1 ]
Hu, Juanjuan [1 ]
Zhao, Wenwen [2 ]
Gao, Xuejiao [2 ]
Jiang, Cuihua [3 ]
Liu, Kang [1 ]
Liu, Baolin [1 ]
Huang, Fang [1 ]
机构
[1] China Pharmaceut Univ, Dept Pharmacol Chinese Mat Med, Nanjing 211198, Jiangsu, Peoples R China
[2] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Peoples R China
[3] Jiangsu Acad Tradit Chinese Med, Lab Translat Med, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Adenosine 5-monophosphate-activated protein kinase; Adipocytes; Akt substrate of 160 kDa; Insulin resistance; Quercetin; GTPASE-ACTIVATING PROTEIN; NECROSIS-FACTOR-ALPHA; GLUCOSE-UPTAKE; SKELETAL-MUSCLE; GLUT4; TRANSLOCATION; KINASE; PHOSPHORYLATION; AKT; HYPERGLYCEMIA; AS160/TBC1D4;
D O I
10.1002/mnfr.201300510
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
ScopeQuercetin 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 resultsThe 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 IB kinase (IKK) 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 AMPK 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. ConclusionQuercetin 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.
引用
收藏
页码:931 / 941
页数:11
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