Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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7-O-Methylaromadendrin Stimulates Glucose Uptake and Improves Insulin Resistance in Vitro
Wei Yun ZhangJung-Jin LeeIn-Su KimYohan KimJeong-Sook ParkChang-Seon Myung
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2010 Volume 33 Issue 9 Pages 1494-1499

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Abstract

The stimulation of glucose uptake into peripheral tissues is an important mechanism for the removal of glucose in blood and for the management of diabetes mellitus (DM). Since recent results have demonstrated the beneficial effects of flavonoids in relation to DM, this study was designed to examine the effects of 7-O-methylaromadendrin (7-O-MA), a flavonoid isolated from Inula viscosa, on glucose uptake into liver and fat tissue, and investigate the molecular mechanisms involved. 7-O-MA at 10 μM significantly stimulated insulin-induced glucose uptake measured by 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) in both human hepatocellular liver carcinoma (HepG2) cells and differentiated 3T3-L1 adipocytes. Adipocyte-specific fatty acid binding protein (aP2) gene expression was increased by 7-O-MA in adipocytes, and both gene and protein level of peroxisome proliferator-activated receptor γ2 (PPARγ2) was also increased. Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5′-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor. Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARγ2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM.

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© 2010 The Pharmaceutical Society of Japan
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