Baicalin ameliorates hepatic insulin resistance and gluconeogenic activity through inhibition of p38 MAPK/PGC-1α pathway
Baicalin ameliorates hepatic insulin resistance and gluconeogenic activity through inhibition of p38 MAPK/PGC-1α pathway
复制标题
黄芩苷通过抑制 p38 MAPK/PGC-1 α 通路改善肝脏胰岛素抵抗和糖异生活性
DOI：
10.1016/j.phymed.2019.153074
复制
发表时间：
2019-11-01
期刊：
影响因子：
7.9
通讯作者：
Bu, Le
中科院分区：
文献类型：
--
作者：
Fang, Penghua;Sun, Yabin;Bu, Le
背景：虽然我们和其他研究结果表明黄芩苷可以增强小鼠骨骼肌和脂肪细胞的葡萄糖摄取和胰岛素敏感性，但黄芩苷对肝脏胰岛素抵抗和糖异生活性的具体代谢贡献尚不清楚。目的：探讨黄芩苷是否参与肝脏胰岛素抵抗和糖异生活性的调节及其机制。研究设计/方法：采用高脂饮食诱导的肥胖小鼠腹腔注射黄芩苷50 mg/kg，每天1次，连续21 d，在胰高血糖素（200 nM）存在下，用黄芩苷（100 μ M）或二甲双胍（100 μ M）处理肝细胞12 h，检测肝组织胰岛素抵抗指标及糖异生相关基因。结果：黄芩苷能降低肥胖小鼠的体重，降低HOMA-IR，减轻高脂饮食引起的葡萄糖耐受不良、高血糖和胰岛素抵抗。黄芩苷显著抑制肥胖小鼠肝脏及肝细胞中p-p38 MAPK、p-CREB、fox01、PGC-1 α、PEPCK和G6Pase的表达。此外，p38MAPK抑制剂也增强了黄芩苷对肝细胞糖异生基因的抑制作用。结论：黄芩苷抑制高脂饮食诱导的肥胖小鼠PGC-1a和糖异生基因的表达，降低糖的产生。黄芩苷主要通过抑制p38 MAPK/PGC-1 α信号通路改善肝脏胰岛素抵抗和糖异生活性。本研究为临床应用黄芩苷治疗高血糖和肝脏胰岛素抵抗提供了可能。
Background: Although the results of our and other studies show that baicalin can enhance glucose uptake and insulin sensitivity in skeletal muscle and adipocytes of mice, the specific metabolic contribution of baicalin on hepatic insulin resistance and gluconeogenic activity is still unclear.Purpose: The aim of this study is to investigate whether baicalin is involved in regulation of hepatic insulin resistance and gluconeogenic activity and its underlying mechanisms.Study Design/Methods: In the present study, high-fat diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 consecutive days, and hepatocytes were treated with baicalin (100 mu M) or metformin (100 mu M) in the presence of glucagon (200 nM) for 12 h. Then insulin resistance indexes and genes related to gluconeogenesis were examined in liver tissues.Results: The present findings showed that baicalin decreased body weight, HOMA-IR, and alleviated high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Furthermore, baicalin markedly suppressed p-p38 MAPK, p-CREB, FoxO1, PGC-1 alpha, PEPCK and G6Pase expression in liver of obese mice and hepatocytes. Moreover, inhibition of gluconeogenic genes by baicalin was also strengthened by p38MAPK inhibitor in hepatocytes.Conclusion: Baicalin suppressed expression of PGC-1a and gluconeogenic genes, and reduced glucose production in high-fat diet-induced obese mice. Baicalin ameliorated hepatic insulin resistance and gluconeogenic activity mainly through inhibition of p38 MAPK/PGC-1 alpha signal pathway. This study provides a possibility of using baicalin to treat hyperglycemia and hepatic insulin resistance in clinic.