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整合代谢组学和转录组学分析揭示金芪降糖片治疗 2 型糖尿病的作用及机制。

Integrated metabolomic and transcriptomic analysis reveals the effects and mechanisms of Jinqi Jiangtang tablets on type 2 diabetes.

机构信息

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.

State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China.

出版信息

Phytomedicine. 2024 Nov;134:155957. doi: 10.1016/j.phymed.2024.155957. Epub 2024 Aug 18.

DOI:10.1016/j.phymed.2024.155957
PMID:39181101
Abstract

BACKGROUND

Type 2 diabetes (T2DM) is one of the major metabolic diseases and poses a serious challenge to human life and global economic development. Jinqi Jiangtang Tablets (JQJT) is effective in ameliorating the effects of T2DM, but the mechanism of JQJT is unclear.

PURPOSE

This study integrated metabolomics and transcriptomics to reveal the mechanism by which JQJT improves T2DM.

METHODS

The T2DM mouse model was established, and the effects of JQJT on improving T2DM were evaluated by determining the levels of blood lipids, fasting blood glucose (FBG), insulin metabolism and hepatic lipid accumulation in mice after JQJT administration for 8 weeks. Serum metabolites were detected using ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS) technology, and mouse liver differential genes were detected using transcriptomic technology. Correlation analysis was used to extract metabolites and RNA with correlations, and potential pathways were enriched and constructed using the common pathway analysis function of MetaboAnalyst 5.0. Finally, the expression of key target proteins and genes was verified by Western blot (WB) and Polymerase Chain Reaction (PCR) to further elucidate the mechanism by which JQJT improves T2DM.

RESULTS

JQJT reduced FBG and lipid levels, improved insulin resistance (IR) and hepatic lipoatrophy in mice. A total of 35 differentially abundant metabolites were identified by metabolomics, and 328 differential genes were detected by transcriptomics. The integrated metabolomics and transcriptomics results suggested that JQJT may ameliorate T2DM mainly by regulating glucose and lipid metabolic pathways. WB and PCR results showed that JQJT regulates the insulin signaling pathway, involved in fatty acid metabolism, glycogen synthesis and catabolism.

CONCLUSIONS

JQJT improved IR in T2DM mice by regulating the insulin signaling pathway, improving glycogen synthesis and glycolysis, and increasing hepatic triglyceride and fatty acid metabolism.

摘要

背景

2 型糖尿病(T2DM)是一种主要的代谢性疾病,对人类生命和全球经济发展构成严重挑战。金芪降糖片(JQJT)在改善 T2DM 方面具有疗效,但 JQJT 的作用机制尚不清楚。

目的

本研究整合代谢组学和转录组学,揭示 JQJT 改善 T2DM 的作用机制。

方法

建立 T2DM 小鼠模型,通过测定 JQJT 给药 8 周后小鼠血脂、空腹血糖(FBG)、胰岛素代谢和肝脂质堆积水平,评价 JQJT 改善 T2DM 的作用。采用超高效液相色谱/四极杆飞行时间串联质谱(UPLC-Q-TOF-MS)技术检测血清代谢物,转录组技术检测小鼠肝差异基因。采用相关分析提取具有相关性的代谢物和 RNA,利用 MetaboAnalyst 5.0 的共同通路分析功能富集和构建潜在通路。最后,采用 Western blot(WB)和聚合酶链反应(PCR)验证关键靶蛋白和基因的表达,进一步阐明 JQJT 改善 T2DM 的作用机制。

结果

JQJT 降低了 FBG 和血脂水平,改善了小鼠的胰岛素抵抗(IR)和肝脂减少。通过代谢组学鉴定出 35 种差异丰度代谢物,通过转录组学检测到 328 个差异基因。整合代谢组学和转录组学结果表明,JQJT 可能主要通过调节葡萄糖和脂质代谢途径改善 T2DM。WB 和 PCR 结果表明,JQJT 通过调节胰岛素信号通路,参与脂肪酸代谢、糖原合成和分解,调节 T2DM 小鼠的胰岛素信号通路。

结论

JQJT 通过调节胰岛素信号通路,改善糖原合成和糖酵解,增加肝甘油三酯和脂肪酸代谢,改善 T2DM 小鼠的 IR。

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