Berberine modulates insulin signaling transduction in insulin-resistant cells
Berberine modulates insulin signaling transduction in insulin-resistant cells
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DOI：
10.1016/j.mce.2009.12.027
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发表时间：
2010-04-12
影响因子：
4.1
通讯作者：
Tong, Peter C. Y.
中科院分区：
文献类型：
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作者：
Liu, Li-Zhong;Cheung, Stanley C. K.;Tong, Peter C. Y.
小檗碱具有胰岛素增敏作用，但其分子机制尚不清楚。在这项工作中，我们研究了小檗碱对胰岛素敏感和胰岛素抵抗大鼠骨骼肌细胞中胰岛素诱导的信号转导和葡萄糖摄取的影响。小檗碱可增加正常细胞AMPK和PKC zeta活性及AS 160磷酸化，但对PKB活性影响不大。在胰岛素抵抗状态下，小檗碱对胰岛素诱导的葡萄糖摄取和GLUT 4转位具有协同作用。小檗碱改善胰岛素诱导的IRS-1酪氨酸磷酸化和p85向IRS-1的募集。这些变化伴随着胰岛素诱导的PKC zeta和PKB活性的增强和肌动蛋白重塑。改善胰岛素信号转导与小檗碱抑制mTOR有关，小檗碱减弱IRS-1的丝氨酸磷酸化。这些结果提示小檗碱可能通过调节胰岛素信号通路中的关键分子，导致胰岛素抵抗细胞葡萄糖摄取增加，从而克服胰岛素抵抗。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
Berberine has been shown to have insulin-sensitizing effect, but the molecular mechanism underlying remains elusive. In this work, we investigated the effect of berberine on insulin-induced signal transduction and glucose uptake in both insulin-sensitive and insulin-resistant rat skeletal muscle cells. Berberine increased the activity of AMPK and PKC zeta and AS 160 phosphorylation in normal cells, but had little effect on PKB activation. In insulin-resistant state, berberine exhibited synergistic effect on insulin-induced glucose uptake and GLUT4 translocation. Berberine improved insulin-induced tyrosine-phosphorylation of IRS-1 and the recruitment of p85 to IRS-1. These changes were accompanied by enhancement in insulin-induced PKC zeta and PKB activity and actin remodeling. The ameliorated insulin signal transduction was related to the inhibition of mTOR by berberine, which attenuated serine-phosphorylation of IRS-1. These results suggest that berberine may overcome insulin resistance via modulating key molecules in insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.