@article{oai:kanazawa-u.repo.nii.ac.jp:00027024,
 author = {Nomura, Masaaki and Takahashi, Tatsuro and Nagata, Naoto and Tsutsumi, Kikue and Kobayashi, Shinjiro and Akiba, Tetsuo and Yokogawa, Koichi and Moritani, Shuzo and Miyamoto, Ken-ichi},
 issue = {7},
 journal = {Biological and Pharmaceutical Bulletin},
 month = {Jul},
 note = {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., 金沢大学附属病院薬剤部},
 pages = {1403--1409},
 title = {Inhibitory mechanisms of flavonoids on insulin-stimulated glucose uptake in MC3T3-G2/PA6 adipose cells},
 volume = {31},
 year = {2008}
}