Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong, China.
Mol Cell Endocrinol. 2010 Apr 12;317(1-2):148-53. doi: 10.1016/j.mce.2009.12.027. Epub 2009 Dec 29.
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 PKCzeta and AS160 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 PKCzeta 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.
小檗碱具有胰岛素增敏作用，但其中的分子机制尚不清楚。在这项研究中，我们研究了小檗碱对胰岛素诱导的信号转导和葡萄糖摄取的影响，分别在胰岛素敏感和胰岛素抵抗的大鼠骨骼肌细胞中进行。小檗碱增加了正常细胞中 AMPK 和 PKCzeta 的活性以及 AS160 的磷酸化，但对 PKB 的激活几乎没有影响。在胰岛素抵抗状态下，小檗碱表现出与胰岛素诱导的葡萄糖摄取和 GLUT4 易位的协同作用。小檗碱改善了胰岛素诱导的 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 PKCzeta 和 PKB 活性以及肌动蛋白重塑的增强。胰岛素信号转导的改善与小檗碱对 mTOR 的抑制有关，它减弱了 IRS-1 的丝氨酸磷酸化。这些结果表明，小檗碱可能通过调节胰岛素信号通路中的关键分子来克服胰岛素抵抗，从而增加胰岛素抵抗细胞的葡萄糖摄取。
