Quercetin and its metabolite isorhamnetin promote glucose uptake through different signalling pathways in myotubes

Scientific Reports
Hao JiangHitoshi Ashida

Abstract

Quercetin and its metabolite isorhamnetin elicit various beneficial effects on human health. However, their bioavailability is low. In this study, we investigated whether low concentrations in the physiological range could promote glucose uptake in L6 myotubes, as well as the underlying molecular mechanisms. We found that 0.1 nM and 1 nM quercetin or 1 nM isorhamnetin significantly increased glucose uptake via translocation of glucose transporter type 4 (GLUT4) to the plasma membrane of L6 myotubes. Quercetin principally activated the CaMKKβ/AMPK signalling pathway at these concentrations, but also activated IRS1/PI3K/Akt signalling at 10 nM. In contrast, 1 nM and 10 nM isorhamnetin principally activated the JAK/STAT pathway. Treatment with siAMPKα and siJAK2 abolished quercetin- and isorhamnetin-induced GLUT4 translocation, respectively. However, treatment with siJAK3 did not affect isorhamnetin-induced GLUT4 translocation, indicating that isorhamnetin induced GLUT4 translocation mainly through JAK2, but not JAK3, signalling. Thus, quercetin preferably activated the AMPK pathway and, accordingly, stimulated IRS1/PI3K/Akt signalling, while isorhamnetin activated the JAK2/STAT pathway. Furthermore, after oral administration of q...Continue Reading

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Citations

Oct 5, 2019·International Journal of Molecular Sciences·Enrique Gamero-EstevezAimee K Ryan
Sep 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sonia Marlen Escandón-RiveraAdolfo Andrade-Cetto
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Dec 2, 2020·International Journal of Molecular Sciences·Jasminka GiacomettiSnježana Bajek
Feb 13, 2021·International Journal of Molecular Sciences·Itziar EseberriMaria P Portillo
May 18, 2021·Frontiers in Pharmacology·Sha LiYibin Feng
Jul 3, 2021·International Journal of Molecular Sciences·Tohru HiraHiroshi Hara
Jul 29, 2021·Preventive Nutrition and Food Science·Jarinyaporn NaowabootSuvara Wattanapitayakul
Nov 17, 2020·Journal of Agricultural and Food Chemistry·Tomoya KitakazeHitoshi Ashida

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Methods Mentioned

BETA
GTPase
electrophoresis

Software Mentioned

ImageJ
JMP

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