Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells
Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells
复制标题
DOI：
10.1248/bpb.b15-00591
复制
发表时间：
2016-04-01
影响因子：
2
通讯作者：
Yin, Zhongyi
中科院分区：
文献类型：
--
作者：
Guo, Lixia;Zheng, Xuxu;Yin, Zhongyi
栀子苷是栀子中的主要化合物之一，具有多种药理活性，但其抗高血糖活性尚未得到充分的研究。本研究旨在首次确定栀子花中的京尼平苷如何调节肝脏葡萄糖生成及其潜在机制。在体外研究中，我们发现京尼平苷对肝糖生成的抑制作用部分是通过活化AMPK激活HepG2细胞。京尼平苷以剂量依赖的方式显著抑制肝葡萄糖的产生。不同浓度的京尼平苷刺激AMPK、乙酰辅酶A合成酶（ACC）和叉头盒类O1 （FoxO1）磷酸化。此外，磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6Pase）活性均被显著抑制。重要的是，通过(1)化合物C（一种选择性AMPK抑制剂）对AMPK活性的抑制，以及(2)小干扰RNA （siRNA）对AMPK α表达的抑制，这些效应被部分逆转。总之，京尼平苷可能通过调节AMPK fox01信号通路抑制肝脏糖异生来改善高血糖。京尼平苷或含京尼平苷的药用植物可能是预防2型糖尿病糖异生的一种有前景的治疗药物。
Geniposide is one of the main compounds in Gardenia jasminoides ELLIS and has many pharmacological activities, but its anti-hyperglycemic activity has not yet been fully explored. This study was designed to determine, for the first time, how geniposide from G. jasminoides regulates hepatic glucose production, and the underlying mechanisms. During in vitro study, we found the inhibitory effect of geniposide on the hepatic glucose production is partly through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Geniposide significantly inhibited hepatic glucose production in a dose-dependent manner. AMPK, acetyl coenzyme A synthetase (ACC) and forkhead box class O1 (FoxO1) phosphorylation were stimulated by different concentrations of geniposide. In addition, the enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were all significantly suppressed. What is important is that these effects were partly reversed by (1) inhibition of AMPK activity by compound C, a selective AMPK inhibitor, and by (2) suppression of AMPK alpha expression by small interfering RNA (siRNA). In summary, geniposide potentially ameliorates hyperglycemia through inhibition of hepatic gluconeogenesis by modulation of the AMPK FoxO1 signaling pathway. Geniposide or geniposide-containing medicinal plants could represent a promising therapeutic agent to prevent type 2 diabetes on gluconeogenesis.