Stimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK

Stimulation of muscle cell glucose uptake by resveratrol through sirtuins and AMPK
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DOI:
10.1016/j.bbrc.2008.06.104
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发表时间:
2008-09-12
影响因子:
3.1
通讯作者:
Tsiani, Evangelia
Tsiani, Evangelia
中科院分区:
生物学4区
文献类型:
--
作者:
Breen, Danna M.;Sanli, Toran;Tsiani, Evangelia

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尽管最近的体外和体内研究表明多酚白藜芦醇 (RSV) 具有抗糖尿病特性,但其具体机​​制尚不清楚。在本研究中,我们研究了 RSV 的影响以及骨骼肌细胞葡萄糖摄取的调节机制。在 L6 肌管中,RSV (100 μM) 诱导葡萄糖 (2DG) 摄取的最大刺激(对照的 201 +/- 8.90%,p < 0.001),这种效应与胰岛素作用相似。 RSV 刺激的葡萄糖摄取被 AMPK 抑制所消除。在 Sirtuin 抑制剂烟酰胺存在的情况下,RSV 刺激的 2DG 摄取和 AMPK 磷酸化被消除。 RSV 不会刺激 GLUT4 或 GLUT1 转运蛋白的显着易位。然而,茚地那韦(一种 GLUT4 特异性抑制剂)治疗可阻断 RSV 刺激的葡萄糖摄取。我们认为 RSV 通过一种涉及去乙酰化酶和 AMPK 的机制来提高肌肉细胞中的葡萄糖摄取,并可能刺激 GLUT4 转运蛋白的内在活性。 (C) 2008 Elsevier Inc. 保留所有权利。
Although recent studies in vitro and in vivo indicate that the polyphenol resveratrol (RSV) has anti-diabetic properties, the exact mechanisms involved are not known. In the present study, we examined the effects of RSV and the mechanism of regulation of glucose uptake in skeletal muscle cells. In L6 myotubes RSV (100 mu M) induced maximum stimulation of glucose (2DG) uptake (201 +/- 8.90% of control, p < 0.001), an effect that was similar to insulin action. RSV-stimulated glucose uptake was abolished by AMPK inhibition. In the presence of the sirtuin inhibitor nicotinamide, RSV-stimulated 2DG uptake and AMPK phosphorylation were abolished. RSV did not stimulate significant translocation of GLUT4 or GLUT1 transporters. However, treatment with indinavir, a GLUT4 specific inhibitor, blocked RSV-stimulated glucose uptake. We propose that RSV elevates glucose uptake in muscle cells through a mechanism that involves sirtuins and AMPK and possibly stimulation of GLUT4 transporter intrinsic activity. (C) 2008 Elsevier Inc. All rights reserved.