Qiyu Granules ameliorate insulin resistance via modulating PI3K/AKT/FoxO1 pathway and AMPK/PPARγ pathway in diabetic KKAy mice

IF 1.2 4区 化学 Q4 CHEMISTRY, ANALYTICAL Chinese Journal of Analytical Chemistry Pub Date : 2025-02-01 DOI:10.1016/j.cjac.2024.100489
Xiaoxu FAN , Jiaqi LIU , Jian HUA, Zhen WANG, Yiwei SHEN, Danyue SHAO, Zhenhui JIN, Jingxia WANG
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Abstract

Objective

To investigate the protective effect and mechanism of Qiyu Granules in alleviating insulin resistance in KKAy mice.

Methods

The chemical ingredients of Qiyu Granules were analyzed using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology and animal experiments were used to verify the pharmacological effects of Qiyu Granules in alleviating insulin resistance in diabetic KKAy mice and to explore its mechanism of action. High-sugar, high-fat chow was fed to KKAy mice for modeling. After 12 weeks, indicators of glucose metabolism (FBG, AUC), lipid metabolism (TC, TG, LDL, HDL, FFA), liver function (ALT, AST) and insulin resistance (FINS, HOMA-IR, HOMA-β, ISI) were detected. Pathological changes in pancreatic and liver tissues were observed by hematoxylin-eosin (H&E) and Oil Red O staining. Hepatic glycogen levels were analyzed using enzyme-linked immunosorbent assay (ELISA) method and periodic acid-Schiff (PAS) staining. Western blot was used to detect the protein expression levels of InsR, p-PI3 K, p-AKT, FoxO1, PEPCK, G6pase, p-AMPK, p-GSK-3β, GLUT2, PPARγ and PPARα.

Results

FBG, AUC, HOMA-IR, TC, TG, LDL, FFA, ALT, AST and hepatic index were decreased in mice treated with Qiyu Granules; while FINS, HOMA-β, ISI, HDL and hepatic glycogen content were increased. Qiyu Granules also improved histopathological changes in the pancreas and liver of KKAy mice. Besides, Qiyu Granules up-regulated the expression levels of InsR, p-PI3 K, p-AKT, p-AMPK, GLUT2 and PPARα proteins in the livers of mice in the model group. However, Qiyu Granules down-regulated the expression levels of FoxO1, PEPCK, G6Pase, p-GSK-3β and PPARγ proteins.

Conclusion

Qiyu Granules may regulate the InsR/PI3K/AKT/FoxO1 pathway, AMPK pathway, and PPARγ/PPARα pathway to ameliorate insulin resistance. Therefore, Qiyu Granules is a promising hypoglycaemic agent for the treatment of DM.

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来源期刊
CiteScore
3.60
自引率
25.00%
发文量
17223
审稿时长
35 days
期刊介绍: Chinese Journal of Analytical Chemistry(CJAC) is an academic journal of analytical chemistry established in 1972 and sponsored by the Chinese Chemical Society and Changchun Institute of Applied Chemistry, Chinese Academy of Sciences. Its objectives are to report the original scientific research achievements and review the recent development of analytical chemistry in all areas. The journal sets up 5 columns including Research Papers, Research Notes, Experimental Technique and Instrument, Review and Progress and Summary Accounts. The journal published monthly in Chinese language. A detailed abstract, keywords and the titles of figures and tables are provided in English, except column of Summary Accounts. Prof. Wang Erkang, an outstanding analytical chemist, academician of Chinese Academy of Sciences & Third World Academy of Sciences, holds the post of the Editor-in-chief.
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