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Nutr Res. 2015 Jul;35(7):618-25. doi: 10.1016/j.nutres.2015.05.010. Epub 2015 May 30.

Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes.

Author information

1
Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan. Electronic address: mohta@kobepharma-u.ac.jp.
2
Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan.
3
Department of Bioanalytical Chemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan.
4
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
5
Department of Complementary and Alternative Medicine, Clinical R&D, Kanazawa University of Graduate School of Medical Science, Kanazawa, 920-8640, Japan.
6
Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
7
Japan Bio Science Laboratory, Osaka, 553-0003, Japan.
8
Institute of Bio-Response Informatics, Kyoto, 602-8566, Japan.

Abstract

4-Hydroxyderricin (4HD) and xanthoangelol (XAG) are major components of n-hexane/ethyl acetate (5:1) extract of the yellow-colored stem juice of Angelica keiskei. 4-Hydroxyderricin and XAG have been reported to increase glucose transporter 4 (GLUT4)-dependent glucose uptake in 3T3-L1 adipocytes, but the detailed mechanism of this phenomenon remains unknown. This present study was aimed at clarifying the detailed mechanism by which 4HD and XAG increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes. Both 4HD and XAG increased glucose uptake and GLUT4 translocation to the plasma membrane. 4-Hydroxyderricin and XAG also stimulated the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase. In addition, phosphorylation of liver kinase B1 (LKB1), which acts upstream of AMPK, was also increased by 4HD and XAG treatment. Small interfering RNA knockdown of LKB1 attenuated 4HD- and XAG-stimulated AMPK phosphorylation and suppressed glucose uptake. These findings demonstrate that 4HD and XAG can increase GLUT4-dependent glucose uptake through the LKB1/AMPK signaling pathway in 3T3-L1 adipocytes.

KEYWORDS:

4-Hydroxyderricin; Chalcones; GLUT4; Glucose uptake; LKB1/AMPK signaling; Xanthoangelol

PMID:
26077869
DOI:
10.1016/j.nutres.2015.05.010
[Indexed for MEDLINE]

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