Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes
Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes
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DOI：
10.1248/bpb.30.2120
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发表时间：
2007-11-01
影响因子：
2
通讯作者：
Hyun, Chang-Kee
中科院分区：
文献类型：
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作者：
Kim, So Hui;Shin, Eun-Jung;Hyun, Chang-Kee
近年来人们发现，小檗碱是一种药用植物生物碱，具有抗高血糖作用。为了探索这种效应的机制，我们使用3 T3-L1脂肪细胞来分析有助于葡萄糖转运的信号通路。小檗碱处理3 T3-L1脂肪细胞6 h后，在正常和胰岛素抵抗状态下，基础葡萄糖摄取均增加，但对胰岛素刺激的葡萄糖摄取无明显增加。渥曼青霉素对磷脂酰肌醇3-激酶（PI 3-K）的抑制并不影响小檗碱对基础葡萄糖摄取的作用。小檗碱不增加胰岛素受体（IR）和胰岛素受体底物（IRS）-1的酪氨酸磷酸化。此外，小檗碱对胰岛素敏感的下游激酶，非典型蛋白激酶C（PKC zeta/lambda）的活性没有影响。然而，有趣的是，细胞外信号调节激酶（ERK），这已被称为是负责葡萄糖转运蛋白（GLUT）I的表达，显着激活小檗碱处理的3 T3-L1细胞。正如预期的那样，GLUT 1蛋白的水平在正常和胰岛素抵抗细胞中对小檗碱的反应都增加。小檗碱对正常细胞和胰岛素抵抗细胞GLUT 4的表达无影响。此外，小檗碱处理增加了3 T3-L1细胞中AMP活化蛋白激酶（AMPK）的活性，据报道这与GLUT 1介导的葡萄糖摄取有关。总之，我们得出结论，小檗碱通过增强GLUT 1表达增加3 T3-L1脂肪细胞的葡萄糖转运活性，并通过激活GLUT 1（AMPK刺激的结果）刺激GLUT 1介导的葡萄糖摄取。
It has recently been known that berberine, an alkaloid of medicinal plants, has anti-hyperglycemic effects. To explore the mechanism underlying this effect, we used 3T3-L1 adipocytes for analyzing the signaling pathways that contribute to glucose transport. Treatment of berberine to 3T3-L1 adipocytes for 6 h enhanced basal glucose uptake both in normal and in insulin-resistant state, but the insulin-stimulated glucose uptake was not augmented significantly. Inhibition of phosphatidyllinositol 3-kinase (PI 3-K) by wortmannin did not affect the berberine effect on basal glucose uptake. Berberine did not augment tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate (IRS)-1. Further, berberine had no effect on the activity of the insulin-sensitive downstream kinase, atypical protein kinase C (PKC zeta/lambda). However, interestingly, extracellular signal-regulated kinases (ERKs), which have been known to be responsible for the expression of glucose transporter (GLUT)I, were significantly activated in berberine-treated 3T3-L1 cells. As expected, the level of GLUT1 protein was increased both in normal and insulin-resistant cells in response to berberine. But berberine affected the expression of GLUT4 neither in normal nor in insulin-resistant cells. In addition, berberine treatment increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 cells, which has been reported to be associated with GLUT1-mediated glucose uptake. Together, we concluded that berberine increases glucose transport activity of 3T3-L1 adipocytes by enhancing GLUT1 expression and also stimulates the GLUT1-mediated glucose uptake by activating GLUT1, a result of AMPK stimulation.