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Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes.
Mol Nutr Food Res. 2014 May; 58(5):931-41.MN

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, P. R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24343960

Citation

Xu, Manli, et al. "Quercetin Differently Regulates Insulin-mediated Glucose Transporter 4 Translocation Under Basal and Inflammatory Conditions in Adipocytes." Molecular Nutrition & Food Research, vol. 58, no. 5, 2014, pp. 931-41.
Xu M, Hu J, Zhao W, et al. Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes. Mol Nutr Food Res. 2014;58(5):931-41.
Xu, M., Hu, J., Zhao, W., Gao, X., Jiang, C., Liu, K., Liu, B., & Huang, F. (2014). Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes. Molecular Nutrition & Food Research, 58(5), 931-41. https://doi.org/10.1002/mnfr.201300510
Xu M, et al. Quercetin Differently Regulates Insulin-mediated Glucose Transporter 4 Translocation Under Basal and Inflammatory Conditions in Adipocytes. Mol Nutr Food Res. 2014;58(5):931-41. PubMed PMID: 24343960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quercetin differently regulates insulin-mediated glucose transporter 4 translocation under basal and inflammatory conditions in adipocytes. AU - Xu,Manli, AU - Hu,Juanjuan, AU - Zhao,Wenwen, AU - Gao,Xuejiao, AU - Jiang,Cuihua, AU - Liu,Kang, AU - Liu,Baolin, AU - Huang,Fang, Y1 - 2013/12/17/ PY - 2013/07/13/received PY - 2013/09/26/revised PY - 2013/10/01/accepted PY - 2013/12/18/entrez PY - 2013/12/18/pubmed PY - 2014/12/17/medline KW - Adenosine 5′-monophosphate-activated protein kinase KW - Adipocytes KW - Akt substrate of 160 kDa KW - Insulin resistance KW - Quercetin SP - 931 EP - 41 JF - Molecular nutrition & food research JO - Mol Nutr Food Res VL - 58 IS - 5 N2 - 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. SN - 1613-4133 UR - https://www.unboundmedicine.com/medline/citation/24343960/Quercetin_differently_regulates_insulin_mediated_glucose_transporter_4_translocation_under_basal_and_inflammatory_conditions_in_adipocytes_ L2 - https://doi.org/10.1002/mnfr.201300510 DB - PRIME DP - Unbound Medicine ER -