Puerarin attenuates endothelial insulin resistance through inhibition of inflammatory response in an IKK尾/IRS-1-dependent manner

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• 作者：Fang Huang^a ; Kang Liu^a ; Hang Du^a ; Junping Kou^b ; Baolin Liu^a ; ^{zhongyao440@163.com} ; ^{njlbl55@sohu.com}
• 关键词：Puerarin ; Endothelial dysfunction ; Inflammation ; Insulin resistance
• 刊名：Biochimie
• 出版年：2012
• 期刊代码：24_03009084
• 类别：bio
• 出版时间：May, 2012
• 卷：94
• 期：5
• 页码：1143-1150
• 文件大小：947 K

摘要

Puerarin is an isoflavonoid isolated from the root of the plant Pueraria lobata and has been used as a prescribed drug in China for the treatment of cardiovascular diseases in the clinical practice. Puerarin possesses potential therapeutic activities for metabolic and cardiovascular disorders. However, little is yet known about its bioprotection against endothelial dysfunction insulin resistance involved. In this study, we established insulin resistance by palmitate stimulation in the endothelium and investigated the action of puerarin on the modulation of insulin sensitivity under the insulin resistant condition. Palmitate stimulation impaired insulin-mediated vasodilation in the rat aorta and puerarin treatment effectively restored the impaired vasodilation in a concentration-dependent manner (1, 10 and 50聽渭M). Palmitate stimulation evoked inflammatory response in endothelial cells. Puerarin inhibited IKK尾/NF-魏B activation and decreased TNF-伪 and IL-6 production with the downregulation of relative gene overexpression. Palmitate stimulation impaired the insulin PI3K signaling pathway and reduced insulin-mediated NO production in endothelial cells. Puerarin attenuated PA-induced phosphorylation of insulin receptor substrate-1 (IRS-1) at S307 and effectively ameliorated insulin-mediated tyrosine phosphorylation of IRS-1. The beneficial modification of serine/tyrosine phosphorylation of IRS-1 restored downstream Akt/eNOS activation, and thereby increased insulin-mediated NO production. These results suggest that puerarin inhibits inflammation and attenuates endothelial insulin resistance in an IKK尾/IRS-1-dependent manner.