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黄芩苷对饮食诱导肥胖小鼠脂肪细胞中葡萄糖转运蛋白4转位的影响

Effect of Baicalein on GLUT4 Translocation in Adipocytes of Diet-Induced Obese Mice.

作者信息

Min Wen, Wu Mingjie, Fang Penghua, Yu Mei, Shi Mingyi, Zhang Zhenwen, Bo Ping

机构信息

Department of Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.

Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, China.

出版信息

Cell Physiol Biochem. 2018;50(2):426-436. doi: 10.1159/000494154. Epub 2018 Oct 11.

Abstract

BACKGROUND/AIMS: Although baicalein has been shown to increase insulin sensitivity in liver of mice, there is no literature available about the effect of baicalein on glucose transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of diet-induced obese mice.

METHODS

In the present study, the obese model was induced in mice fed a high fat diet (20% carbohydrates, 21% protein and 59% fat) for 16 weeks. The diet-induced obese mice were given 20mg/kg baicalein intraperitoneally (i.p.) once a day for 21 days. The plasma insulin was measured by enzyme-linked immunosorbent assay. Fasting blood glucose and insulin resistance indexes were measured by glucose tolerance test (GTT). The expression levels of PGC-1α, UCP1, GLUT4, PPARγ, pP38MAPK, pERK and pAKT in adipocytes were determined by quantitative real-time polymerase chain reaction and western blotting.

RESULTS

The present findings showed that administration of baicalein decreased pP38MAPK, pERK and PPARγ levels, but enhanced pAKT, PGC-1α and UCP1 contents as well as GLUT4 expression in adipocytes, and reversed high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Moreover, baicalein treatment increased GLUT4 concentration in plasma membranes of adipocytes, i.e. baicalein may prevent insulin resistance through the GLUT4 translocation from intracellular membrane compartments to plasma membranes in adipocytes.

CONCLUSION

These results suggest that baicalein is a powerful and promising agent for treatment of obesity and insulin resistance via Akt/GLUT4 pathway.

摘要

背景/目的:尽管已证实黄芩素可提高小鼠肝脏的胰岛素敏感性,但尚无关于黄芩素对饮食诱导肥胖小鼠脂肪细胞中葡萄糖转运蛋白4(GLUT4)从细胞内膜池转位至质膜影响的文献报道。

方法

在本研究中,通过给小鼠喂食高脂饮食(20%碳水化合物、21%蛋白质和59%脂肪)16周诱导肥胖模型。给饮食诱导肥胖小鼠每天腹腔注射(i.p.)20mg/kg黄芩素,持续21天。采用酶联免疫吸附测定法测量血浆胰岛素。通过葡萄糖耐量试验(GTT)测量空腹血糖和胰岛素抵抗指数。采用定量实时聚合酶链反应和蛋白质免疫印迹法测定脂肪细胞中PGC-1α、UCP1、GLUT4、PPARγ、pP38MAPK、pERK和pAKT的表达水平。

结果

本研究结果表明,黄芩素给药可降低脂肪细胞中pP38MAPK、pERK和PPARγ水平,但可提高pAKT、PGC-1α和UCP1含量以及GLUT4表达,并逆转饮食诱导肥胖小鼠中高脂饮食诱导的葡萄糖不耐受、高血糖和胰岛素抵抗。此外,黄芩素处理可增加脂肪细胞质膜中GLUT4浓度,即黄芩素可能通过促进GLUT4从脂肪细胞内的膜区室转位至质膜来预防胰岛素抵抗。

结论

这些结果表明,黄芩素是一种通过Akt/GLUT4途径治疗肥胖和胰岛素抵抗的有效且有前景的药物。

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