Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells

フォーマット:

論文

責任表示:

Nomura, Masaaki ; Takahashi, Tatsuro ; Nagata, Naoto ; Tsutsumi, Kikue ; Kobayashi, Shinjiro ; Akiba, Tetsuo ; Yokogawa, Koichi ; Moritani, Shuzo ; Miyamoto, Ken-ichi

言語:

英語

出版情報:

日本薬学会, 2008-07-01

著者名:

Nomura, Masaaki

Takahashi, Tatsuro

Nagata, Naoto

Tsutsumi, Kikue

Kobayashi, Shinjiro

Akiba, Tetsuo

Yokogawa, Koichi

Moritani, Shuzo

Miyamoto, Ken-ichi

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掲載情報:

Biological and Pharmaceutical Bulletin

ISSN:

0918-6158      

巻:

31

通号:

7

開始ページ:

1403

終了ページ:

1409

バージョン:

publisher

概要:

金沢大学附属病院薬剤部<br />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. 続きを見る

URL:

http://hdl.handle.net/2297/11553