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基于网络药理学阐明 GF5000 多糖通过调节 GCK 对糖尿病大鼠的降血糖机制

Network Pharmacology-Based Elucidation of the Hypoglycemic Mechanism of GF5000 Polysaccharides via GCK modulation in Diabetic Rats.

作者信息

Xiao Chun, Jiao Chunwei, Huang Longhua, Hu Huiping, Xie Yizhen, Wu Qingping

机构信息

National Health Commission Science and Technology Innovation Platform for Nutrition and Safety of Microbial Food, Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China.

Guangdong Yuewei Edible Fungi Technology Co., Ltd., Guangzhou 510663, China.

出版信息

Nutrients. 2025 Mar 10;17(6):964. doi: 10.3390/nu17060964.

DOI:10.3390/nu17060964
PMID:40289960
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11944433/
Abstract

BACKGROUND/OBJECTIVES: Our lab has previously reported that (maitake mushroom) GF5000 has antidiabetic potential owing to its ability to improve insulin resistance. This study aimed to gain insight into the system-level hypoglycemic mechanisms of GF5000 using transcriptomics, proteomics, and network pharmacology. This study provides new insights into the hypoglycemic mechanisms of GF5000, identifying key molecular targets involved in mitigating insulin resistance in T2DM.

METHODS

Liver protein and gene expression in normal control (NC), diabetic control (DC), and GF5000-treated (GF5000) rats were analyzed via iTRAQ and RNA-seq. The relationships between differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and type 2 diabetes (T2DM) disease targets were studied using Metascape and the Cytoscape GeneMANIA plug-in.

RESULTS

One hundred and fifty-two DEGs and sixty-two DEPs were identified; twenty DEGs/DEPs exhibited the same trend in mRNA and protein expression levels when comparing the GF5000 vs. DC groups. The Metascape analysis revealed that the T2DM disease targets included four DEGs-, , , and -and two DEPs-glucokinase and acetyl-CoA carboxylase 2. A Cytoscape-GeneMANIA analysis of thirteen DEGs/DEPs related to T2DM showed that /Apolipoprotein A-I, /glucokinase regulatory protein, and /glucokinase had the highest connectivity and centrality in the topological network. The qPCR results confirmed that GF5000 increased the mRNA expression of in -knockdown HepG2 cells.

CONCLUSIONS

These results provide theoretical evidence for the use of GF5000 as a potential active nutritional ingredient for the prevention and treatment of T2DM. Our findings suggest that GF5000 targets multiple pathways implicated in T2DM, offering a multi-faceted approach to disease management and prevention.

摘要

背景/目的:我们实验室之前报道过舞茸GF5000因其改善胰岛素抵抗的能力而具有抗糖尿病潜力。本研究旨在通过转录组学、蛋白质组学和网络药理学深入了解GF5000的系统水平降血糖机制。本研究为GF5000的降血糖机制提供了新见解,确定了参与减轻2型糖尿病(T2DM)胰岛素抵抗的关键分子靶点。

方法

通过iTRAQ和RNA测序分析正常对照(NC)、糖尿病对照(DC)和GF5000处理(GF5000)大鼠的肝脏蛋白质和基因表达。使用Metascape和Cytoscape GeneMANIA插件研究差异表达基因(DEG)、差异表达蛋白质(DEP)与2型糖尿病(T2DM)疾病靶点之间的关系。

结果

鉴定出152个DEG和62个DEP;在比较GF5000组与DC组时,20个DEG/DEP在mRNA和蛋白质表达水平上呈现相同趋势。Metascape分析显示,T2DM疾病靶点包括4个DEG—— 、 、 和 ——以及2个DEP——葡萄糖激酶和乙酰辅酶A羧化酶2。对13个与T2DM相关的DEG/DEP进行的Cytoscape - GeneMANIA分析表明, /载脂蛋白A - I、 /葡萄糖激酶调节蛋白和 /葡萄糖激酶在拓扑网络中具有最高的连通性和中心性。qPCR结果证实,GF5000增加了在 敲低的HepG2细胞中 的mRNA表达。

结论

这些结果为将GF5000用作预防和治疗T2DM的潜在活性营养成分提供了理论证据。我们的研究结果表明,GF5000针对T2DM涉及的多个途径,为疾病管理和预防提供了多方面的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/4b20b16e2b7b/nutrients-17-00964-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/18988b687c0f/nutrients-17-00964-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/7289581da0c6/nutrients-17-00964-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/ea6ddd59bf98/nutrients-17-00964-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/1b2b05f5ea26/nutrients-17-00964-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/b3bc2b6f311c/nutrients-17-00964-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/d292d7c4871f/nutrients-17-00964-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/4b20b16e2b7b/nutrients-17-00964-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/18988b687c0f/nutrients-17-00964-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/7289581da0c6/nutrients-17-00964-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/ea6ddd59bf98/nutrients-17-00964-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/1b2b05f5ea26/nutrients-17-00964-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/b3bc2b6f311c/nutrients-17-00964-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/d292d7c4871f/nutrients-17-00964-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf2/11944433/4b20b16e2b7b/nutrients-17-00964-g007.jpg

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