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タイトル: Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells
著者: Nomura, Masaaki
Takahashi, Tatsuro
Nagata, Naoto
Tsutsumi, Kikue
Kobayashi, Shinjiro
Akiba, Tetsuo
Yokogawa, Koichi
Moritani, Shuzo
Miyamoto, Ken-ichi
宮本, 謙一
発行日: 2008年 7月
出版社(者): 日本薬学会
雑誌名: Biological and Pharmaceutical Bulletin
ISSN: 0918-6158
巻: 31
号: 7
開始ページ: 1403
終了ページ: 1409
キーワード: Adipocyte
Akt
Flavonoid
Glucose transporter 4
Glucose uptake
Insulin
抄録: 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.
DOI: 10.1248/bpb.31.1403
URI: http://hdl.handle.net/2297/11553
資料種別: Journal Article
版表示: publisher
出現コレクション:1. 査読済論文

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