Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes

Ginsenoside Rb1 stimulates glucose uptake through insulin-like signaling pathway in 3T3-L1 adipocytes
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DOI:
10.1677/joe-08-0104
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发表时间:
2008-09-01
影响因子:
4
通讯作者:
Chen, Mingdao
Chen, Mingdao
中科院分区:
医学2区
文献类型:
--
作者:
Shang, Wenbin;Yang, Ying;Chen, Mingdao

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一系列的临床试验和动物实验证明,人参及其主要活性成分人参皂苷具有降糖作用。在我们以前的研究中,已经证明,TRIBRb-1调节过氧化物酶体增殖物激活受体γ活性,以促进3 T3-L1细胞的脂肪生成。然而,Rb-1对胰岛素敏感细胞葡萄糖转运的影响及其分子机制需要进一步阐明。在这项研究中,Rb-1显着刺激基础和胰岛素介导的葡萄糖摄取的时间和剂量依赖性的方式在3 T3-L1脂肪细胞和C2 C12肌管;达到最大效果,在1 μ M的浓度和3小时的时间。在脂肪细胞中,Rb-1促进GLUT 1和GLUT 4易位到细胞表面,这通过分析它们在亚细胞膜组分中的分布来检测,并且使用GLUT 4-绿色荧光蛋白转染中国人卵巢细胞证实了增强的GLUT 4易位。同时,Rb-1增加胰岛素受体底物-1和蛋白激酶B(PK B)的磷酸化,并在胰岛素受体未激活的情况下刺激磷脂酰肌醇3-激酶(PI 3 K)活性。Rb-1诱导的葡萄糖摄取以及GLUT 1和GLUT 4易位被PI 3 K抑制剂抑制。这些结果表明,在胰岛素敏感细胞中,GLUT 1和GLUT 4通过部分激活胰岛素信号通路而促进葡萄糖转运,从而刺激葡萄糖转运。这些发现有助于了解人参和人参皂苷的降血糖和抗糖尿病特性。
A series of clinical trials and animal experiments have demonstrated that ginseng and its major active constituent, ginsenosides, possess glucose-lowering action. In our previous study, ginsenoside Rb-1 has been shown to regulate peroxisome proliferator-activated receptor gamma activity to facilitate adipogenesis of 3T3-L1 cells. However, the effect of Rb-1 on glucose transport in insulin-sensitive cells and its molecular mechanism need further elucidation. In this study, Rb-1 significantly stimulated basal and insulin-mediated glucose uptake in a time- and dose-dependent manner in 3T3-L1 adipocytes and C2C12 myotubes; the maximal effect was achieved at a concentration of 1 mu M and a time of 3 h. In adipocytes, Rb-1 promoted GLUT1 and GLUT4 translocations to the cell surface, which was examined by analyzing their distribution in subcellular membrane fractions, and enhanced translocation of GLUT4 was confirmed using the transfection of GLUT4-green fluorescence protein in Chinese Hamster Ovary cells. Meanwhile, Rb-1 increased the phosphorylation of Insulin receptor substrate-1 and protein kinase B (PKB), and stimulated phosphatidylinositol 3-kinase (PI3K) activity in the absence of the activation of the insulin receptor. Rb-1-induced glucose uptake as well as GLUT1 and GLUT4 translocations was inhibited by the PI3K inhibitor. These results suggest that ginsenoside Rb-1 stimulates glucose transport in insulin-sensitive cells by promoting translocations of GLUT1 and GLUT4 by partially activating the insulin signaling pathway. These findings are useful in understanding the hypoglycemic and anti-diabetic properties of ginseng and ginsenosides.