Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation
Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation
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DOI：
10.1016/j.ejphar.2010.08.021
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发表时间：
2010-12-01
影响因子：
5
通讯作者：
Chang, Tsu-Chung
中科院分区：
文献类型：
--
作者：
Huang, Yu-Chuan;Chang, Wen-Liang;Chang, Tsu-Chung
为了研究茯苓对葡萄糖吸收的影响及其机制，分离并分析了6个羊毛烷型三萜类化合物。其中，厚壁酸对3T3-L1脂肪细胞葡萄糖摄取的刺激作用最为显著。此外，还分析了厚壁酸对分化的3T3-L1脂肪细胞葡萄糖转运蛋白表达谱的影响。我们的结果表明，厚壁酸诱导了GLUT4的表达，但不能诱导GLUT1在mRNA和蛋白水平上的表达。利用慢病毒载体获得的GLUT4短发夹状RNA(ShRNA)进一步证实了GLUT4的作用。当抑制3T3-L1脂肪细胞内源性GLUT4的表达时，厚壁酸对葡萄糖摄取的刺激作用消失。除了增加GLUT4的表达外，厚壁酸还刺激脂肪细胞中GLUT4从细胞内的囊泡到质膜的重分布。将分化的脂肪细胞暴露于厚壁酸可增加胰岛素受体底物(IRS)-1的磷酸化。AKT和AMP激活的激酶(AMPK)。进一步证实了PI3K和AMPK参与了厚壁酸的作用，因为PI3K和AMPK抑制剂完全阻断了厚壁酸介导的脂肪细胞活性。此外，在分化的脂肪细胞中，厚朴酸能诱导甘油三酯的积聚并抑制脂肪分解。综上所述，我们证明了该化合物在促进葡萄糖摄取、GLUT4基因表达和转位以及促进甘油三酯在脂肪细胞中积累方面具有胰岛素样活性。我们的研究为探索蚕豆降血糖作用的潜在机制提供了重要的理论依据。(C)2010爱思唯尔B.V.保留所有权利。
In an effort to investigate the effect and mechanism of Poria cocos on glucose uptake, six lanostane-type triterpenoids were isolated and analyzed. Among them, pachymic acid displayed the most significant stimulating activity on glucose uptake in 3T3-L1 adipocytes. The effect of pachymic acid on the expression profile of glucose transporters in differentiated 3T3-L1 adipocytes was also analyzed. Our results demonstrated that pachymic acid induced an increase in GLUT4, but not GLUT1, expression at both the mRNA and protein levels. The role of GLUT4 was further confirmed using the lentiviral vector-derived GLUT4 short hairpin RNA (shRNA). The stimulating activity of pachymic acid on glucose uptake was abolished when the endogenous GLUT4 expression was suppressed in 3T3-L1 adipocytes. In addition to increased GLUT4 expression, pachymic acid stimulated GLUT4 redistribution from intracellular vesicles to the plasma membrane in adipocytes. Exposure of the differentiated adipocytes to pachymic acid increased the phosphorylation of insulin receptor substrate (IRS)-1. AKT and AMP-activated kinase (AMPK). The involvement of PI3K and AMPK in the action of pachymic acid was further confirmed as PI3K and AMPK inhibitors completely blocked the pachymic acid-mediated activities in adipocytes. In addition, pachymic acid was shown to induce triglyceride accumulation and inhibit lipolysis in differentiated adipocytes. Taken together, we demonstrated the insulin-like activities of this compound in stimulating glucose uptake, GLUT4 gene expression and translocation, and promoting triglyceride accumulation in adipocytes. Our study provides important insights into the underlying mechanism of hypoglycemic activity of P. cocos. (C) 2010 Elsevier B.V. All rights reserved.