Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells
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概要
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We assessed the effects of different classes of flavonoids on insulin-stimulated 2-deoxy-D-[1-3H]glucose uptake by mouse MC3T3-G2/PA6 cells differentiated into mature adipose cells. Among the flavonoids examined, the flavones, apigenin and luteolin, the flavonols, kaempferol, quercetin and fisetin, an isoflavone, genistein, a flavanonol, silybin, and the flavanols, (-)-epigallocatechin gallate (EGCG) and theaflavins, significantly inhibited insulin-stimulated glucose uptake. Key structural features of flavonoids for inhibition of insulin-stimulated glucose uptake are the B-ring 4′- or 3′,4′-OH group and the C-ring C2-C3 double bond of the flavones and flavonols, the A-ring 5-OH of isoflavones, and the galloyl group of EGCG and theaflavins. Luteolin significantly inhibits insulin-stimulated phosphorylation of insulin receptor-β subunit (IR-β ), and apigenin, kaempferol, quercetin and fisetin, also tended to inhibit the IR-β phosphorylation. On the other hand, isoflavones, flavanols or flavanonols did not affect insulin-stimulated IR-β phosphorylation. Apigenin, luteolin, kaempferol, quercetin and fisetin also appeared to inhibit insulin-stimulated activation of Akt, a pivotal downstream effector of phosphatidylinositol 3-kinase (PI3K), and suppressed insulin-dependent translocation of a glucose transporter, (GLUT)4, into the plasma membrane. Although genistein, silybin, EGCG and theaflavins had no effect on the insulin-stimulated activation of Akt, they blocked insulin-dependent GLUT4 translocation. These results provide novel insights into the modulation by flavonoids of insulin's actions, including glucose uptake in adipocytes. © 2008 Pharmaceutical Society of Japan.
- 公益社団法人日本薬学会の論文
- 2008-07-01
著者
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NOMURA Masaaki
Department of Pharmacology and Pharmaceutics, Graduate School of Natural Science and Technology, Kan
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MIYAMOTO Ken-ichi
Department of Pharmacology and Pharmaceutics, Graduate School of Natural Science and Technology, Kan
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Akiba Tetsuo
Department Of Medicinal Informatics Graduate School Of Medical Science Kanazawa University
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Akiba Tetsuo
北陸大学 薬学部臨床薬理学
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KOBAYASHI Shinjiro
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University
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Nomura Masaaki
北陸大学 薬学部臨床薬理学
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Nomura Masaaki
北陸大学 薬学部合成化学
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YOKOGAWA Koichi
Department of Hospital Pharmacy, School of Medicine, Kanazawa University
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Miyamoto K
Department Of Hospital Pharmacy School Of Medicine Kanazawa University:department Of Medicinal Infor
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Nomura Masaaki
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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TAKAHASHI Tatsuo
Department of Surgery, Keio University School of Medicine
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NAGATA NAOTO
Department of Anesthesiology, Miyazaki Medical College
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TSUTSUMI Kikue
Department of Hospital Pharmacy, School of Medicine, Kanazawa University
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MORITANI Shuzo
Department of Nursing, Faculty of Nursing and Welfare, Fukui Prefectural University
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Yokogawa Koichi
Department Of Hospital Pharmacy And Department Of Medicinal Informatics Graduate School Of Medical S
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Kobayashi Shinjiro
Department Of Chemical Pharmacology Toyama Medical And Pharmaceutical University
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Tsutsumi Kikue
Department Of Hospital Pharmacy School Of Medicine Kanazawa University
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Morito Satoshi
Department Of Clinical Pharmacy Graduate School Of Natural Science And Technology Kanazawa Universit
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Moritani Shuzo
Department Of Nursing Faculty Of Nursing And Welfare Fukui Prefectural University
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Moritani Shuzo
Department Of Medical Zoology School Of Medicine Kanazawa University
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Takahashi Tatsuo
Department Of Surgery Keio University School Of Medicine
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Yokogawa Koichi
Department Of Hospital Pharmacy School Of Medicine Kanazawa University:department Of Medicinal Infor
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Yokogawa Koichi
Department Of Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
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Nagata Naoto
Department Of Hospital Pharmacy School Of Medicine Kanazawa University
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Nagata Naoto
Department Of Anesthesiology Miyazaki Medical College
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Miyamoto Ken-ichi
Department Of Applied Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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Noguchi Masamichi
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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Takahashi Tatsuo
Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University
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Nomura Masaaki
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University
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Kobayashi Shinjiro
Department of Applied Chemistry, Faculty of Engineering, Kyushu University
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