Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis.
Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis.
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癸酸钠通过 AMPK 增强小檗碱抑制肝糖异生的降血糖作用
DOI：
10.1016/j.mce.2012.08.006
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发表时间：
2012-11-05
影响因子：
4.1
通讯作者：
Liu, Yanjun
中科院分区：
文献类型：
--
作者：
Zhang, Ming;Lv, Xiaoyan;Li, Jing;Meng, Zhaojie;Wang, Qiujing;Chang, WenGuang;Li, Wei;Chen, Li;Liu, Yanjun
关键词：
小檗碱（BER）是小檗属和黄连属的天然产物和活性成分，已被证明具有抗糖尿病活性。但该药的生物利用度较差，极大地限制了其临床应用。在我们之前的研究中，我们证明了将癸酸钠（一种吸收促进剂）与 BER 共同给药可以显着提高 BER 的生物利用度，而不会造成任何严重的粘膜损伤。在这里，我们研究了 BER 对 AMP 激活蛋白激酶 (AMPK)/糖异生途径的影响以及癸酸钠对 BER 降血糖作用的影响。在高脂饮食和低剂量 STZ 诱导的糖尿病大鼠模型中研究了 BER 与癸酸钠共同给药降低胰岛素抵抗的能力。进行蛋白质印迹以评估 BER 对糖尿病大鼠和 HepG2 肝细胞中参与肝糖异生的 AMPK 信号蛋白的影响。 BER 降低了糖尿病大鼠的体重，并在不改变食物摄入量的情况下显着改善了葡萄糖耐量。同样，BER 降低了糖尿病大鼠的血浆甘油三酯并改善了胰岛素作用。 BER下调肝组织中糖异生关键酶PEPCK和G6Pase升高的表达，抑制TORC2从细胞质到细胞核的易位，并增加肝组织中的AMPK活性。与癸酸钠共同给药时，BER 的效果更高。 BER 处理导致 HepG2 肝细胞中葡萄糖产生减少。 BER 增加 AMPK 活性，减少 PEPCK 以及核转录因子 PGC-1、HNF-4α 和 FOXO1 的表达。 BER 对糖异生的作用可以被 AMPK 抑制剂化合物 C 部分阻断。BER 可以至少部分通过刺激 AMPK 活性来抑制糖尿病大鼠模型中的肝脏糖异生，并且 BER 的这种作用可以通过癸酸钠增强。
Berberine (BER), a natural product and active ingredient of genera Berberis and Coptis, has been demonstrated to possess anti-diabetic activities. However, the poor bioavailability of this agent greatly limits its clinical application. In our previous study, we demonstrated that co-administration of sodium caprate, an absorption enhancer, with BER could significantly increase the bioavailability of BER without any serious mucosal damage. Here, we investigated the effects of BER on AMP-activated protein kinase (AMPK)/gluconeogenesis pathway and the effects of sodium caprate on hypoglycemic action of BER. The ability of BER co-administered with sodium caprate to reduce insulin resistance was investigated in diabetic rat model induced by high-fat diet and low dose STZ. Western blot was performed to evaluate effects of BER on AMPK signaling proteins involved in hepatic gluconeogenesis in diabetic rat and HepG2 hepatocytes. BER reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in diabetic rats. Similarly, BER reduced plasma triglycerides and improved insulin action in diabetic rats. BER down-regulated the elevated expressions of gluconeogenesis key enzymes PEPCK and G6Pase, inhibited the translocation of TORC2 from cytoplasm to nucleus and increased AMPK activity in liver tissues. The effect of BER was higher when co-administered with sodium caprate. BER treatment resulted in reduced glucose production in HepG2 hepatocytes. BER increased AMPK activity, reduced the expression of PEPCK, and the nuclear transcription factors PGC-1, HNF-4α and FOXO1. The effect of BER on gluconeogenesis could be partly blocked by AMPK inhibitor, Compound C. BER could suppress hepatic gluconeogenesis in rat model of diabetes at least in part via stimulation of AMPK activity and this action of BER is augmented by sodium caprate.
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影响因子：
4.1
作者：
Liu, Li-Zhong;Cheung, Stanley C. K.;Tong, Peter C. Y.
通讯作者：
Tong, Peter C. Y.
影响因子：
56.9
作者：
Shaw, RJ;Lamia, KA;Cantley, LC
通讯作者：
Cantley, LC
影响因子：
2.8
作者：
Zeng, XH;Zeng, XJ;Li, YY
通讯作者：
Li, YY
影响因子：
6.5
作者：
Brusq, Jean-Marie;Ancellin, Nicolas;Issandou, Marc
通讯作者：
Issandou, Marc
影响因子：
--
作者：
Zhang, Ming;Lv, Xiao-Yan;Li, Jing;Xu, Zhi-Gang;Chen, Li
通讯作者：
Chen, Li