title: Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes.
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.
authors.affiliation: Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan. Electronic address: mohta@kobepharma-u.ac.jp.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ohta
authors.affiliation: Department of Medical Biochemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Fujinami
authors.affiliation: Department of Bioanalytical Chemistry, Kobe Pharmaceutical University, Kobe, 658-8558, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Amano
authors.affiliation: Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.affiliation: Department of Complementary and Alternative Medicine, Clinical R&D, Kanazawa University of Graduate School of Medical Science, Kanazawa, 920-8640, Japan.
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Department of Complementary and Alternative Medicine, Clinical R&D, Kanazawa University of Graduate School of Medical Science, Kanazawa, 920-8640, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Ito
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Sawada
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Iwasa
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.
authors.forename: Jo
authors.initials: J
authors.lastname: Kitawaki
authors.affiliation: Japan Bio Science Laboratory, Osaka, 553-0003, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Institute of Bio-Response Informatics, Kyoto, 602-8566, Japan.
authors.forename: Muneo
authors.initials: M
authors.lastname: Tsujikawa
authors.affiliation: Institute of Bio-Response Informatics, Kyoto, 602-8566, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Obayashi
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology; D047188:Chalcones / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018547:Plant Stems; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction
chemical_list: D047188:Chalcones; D051275:Glucose Transporter Type 4; D010936:Plant Extracts; D034741:RNA, Small Interfering; C068243:4-hydroxyderricin; D002599:Chalcone; C068244:xanthoangelol; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: 4-Hydroxyderricin; Chalcones; GLUT4; Glucose uptake; LKB1/AMPK signaling; Xanthoangelol