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马钱苷通过PI3K/Akt信号通路抑制FOXO1核转位对INS-1细胞的抗糖尿病作用

Anti-diabetic effect of loganin by inhibiting FOXO1 nuclear translocation via PI3K/Akt signaling pathway in INS-1 cell.

作者信息

Mo Fang-Fang, Liu Hai-Xia, Zhang Yi, Hua Jing, Zhao Dan-Dan, An Tian, Zhang Dong-Wei, Tian Tian, Gao Si-Hua

机构信息

Beijing University of Chinese Medicine, Beijing, 100029, China.

Beijing Open University, Beijing, 100081, China.

出版信息

Iran J Basic Med Sci. 2019 Mar;22(3):262-266. doi: 10.22038/ijbms.2019.30246.7294.

Abstract

OBJECTIVES

JiangTangXiaoKe (JTXK) granule, a Chinese traditional herbal formula, has been clinically used and demonstrated to be beneficial in controlling high glucose and to relieve the symptoms of Type 2 diabetes mellitus patients for decades. In this study, we explored how loganin, one of the components in JTXK granule, mediated the anti-diabetic effect.

MATERIALS AND METHODS

We generate a cell model with the dysfunction of insulin secretion by over-expression FOXO1 in INS-1 cells. MTT method was used to detect cytotoxicity after treated with Loganin. ELISA analysis was used to examine insulin secretion. The expression levels of FOXO1 and Akt were evaluated by Western blot.

RESULTS

Treatment with Loganin did not change the expression level of FOXO1 in INS-1 cells, but increased phosphorylation of FOXO1 and inhibited the nuclear translocation and accumulation of FOXO1, which improved the insulin secretion of the cells. Mechanistically, we found PI3K/Akt signaling pathway involved in these effects, which were blocked by an Akt inhibitor, LY294002.

CONCLUSION

Loganin mediated the subcellular distribution of FOXO1 via PI3K/Akt signaling pathway, which protected the function of insulin secretion in islet INS-1 cells.

摘要

目的

降糖消颗粒是一种中药复方制剂,已临床应用数十年,被证明对控制高血糖和缓解2型糖尿病患者症状有益。在本研究中,我们探讨了降糖消颗粒中的成分之一马钱苷如何介导其抗糖尿病作用。

材料与方法

我们通过在INS-1细胞中过表达FOXO1构建胰岛素分泌功能障碍的细胞模型。采用MTT法检测马钱苷处理后的细胞毒性。采用ELISA分析检测胰岛素分泌。通过蛋白质印迹法评估FOXO1和Akt的表达水平。

结果

马钱苷处理未改变INS-1细胞中FOXO1的表达水平,但增加了FOXO1的磷酸化,抑制了FOXO1的核转位和积累,从而改善了细胞的胰岛素分泌。机制上,我们发现PI3K/Akt信号通路参与了这些作用,而Akt抑制剂LY294002可阻断这些作用。

结论

马钱苷通过PI3K/Akt信号通路介导FOXO1的亚细胞分布,从而保护胰岛INS-1细胞的胰岛素分泌功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc5c/6528715/25a2cc0fb80f/IJBMS-22-262-g001.jpg

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