Berberine improves glucose metabolism through induction of glycolysis
Berberine improves glucose metabolism through induction of glycolysis
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DOI：
10.1152/ajpendo.00211.2007
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发表时间：
2008-01-01
影响因子：
5.1
通讯作者：
Ye, Jianping
中科院分区：
文献类型：
--
作者：
Yin, Jun;Gao, Zhanguo;Ye, Jianping
黄连素是中国地区用于控制2型糖尿病患者血糖的一种植物生物碱，最近有报道称它具有激活AMPK的作用。然而，目前还不清楚黄连素是如何激活AMPK的。本研究对黄连素的体内外活性及作用机制进行了研究。在饮食肥胖的大鼠中，黄连素在给药5周后增加了胰岛素敏感性。空腹胰岛素和HOMA-IR分别下降46%和48%。在包括3T3-L1脂肪细胞、L6肌管、C2C12肌管和H4IIE肝细胞在内的细胞系中，黄连素被发现增加葡萄糖消耗和2-脱氧葡萄糖摄取，并在不依赖胰岛素的情况下在较小程度上增加3-O-甲基葡萄糖(3-OMG)摄取。在IRS-1(Ser(307/312))、Akt、p70S6和ERK磷酸化不发生变化的情况下，黄连素可增强胰岛素诱导的葡萄糖摄取。黄连素作用0.5h后，AMPK的磷酸化增强，并持续至16h。有氧和无氧呼吸测定以了解黄连素的作用机制。AMPK的持续磷酸化与AMP/ATP比值的持续升高和氧耗量的减少有关。随着乳酸产量的增加，糖酵解增加。黄连素无细胞毒性，对细胞培养的L6肌管质膜有保护作用。这些结果表明，黄连素通过刺激糖酵解来促进葡萄糖代谢，这与抑制线粒体中的葡萄糖氧化有关。黄连素诱导的AMPK激活可能是线粒体抑制增加AMP/ATP比率的结果。
Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser(307/312)), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for >= 16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.