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绿豆芽中天然外泌体样纳米颗粒通过激活 PI3K/Akt/GLUT4/GSK-3β 信号通路发挥抗糖尿病作用。

Natural exosomes-like nanoparticles in mung bean sprouts possesses anti-diabetic effects via activation of PI3K/Akt/GLUT4/GSK-3β signaling pathway.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, School of Basic Medical Sciences, School of Health and Rehabilitation, CDUTCM-KEELE Joint Health and Medical Sciences Institute, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.

出版信息

J Nanobiotechnology. 2023 Sep 28;21(1):349. doi: 10.1186/s12951-023-02120-w.

Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance. Mung bean sprouts are traditionally considered a "folk" hypoglycemic food and their pharmacological effects and underlying mechanisms warrant further investigation.

PURPOSE

This study aimed to investigate the anti-diabetic effects of the exosomes-like nanoparticles in mung bean sprouts (MELNs) and explore the related molecular mechanisms.

RESULTS

MELNs were isolated using a differential centrifugation-polyethylene glycol (PEG) method, and the identification of MELNs were confirmed by PAGE gel electrophoresis, agarose gel electrophoresis, thin-layer chromatography (TLC), and transmission electron microscopy (TEM). In the high-fat diet/streptozotocin (HFD/STZ) mouse model, MELNs ameliorated the progression of T2DM by increasing oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results, decreasing the fasting blood glucose level, and reducing the serum triglycerides (TG) and total cholesterol (TC). Histopathological examinations indicated MELNs diminished inflammatory infiltration of hepatocytes and amplified the area of islet B cells. In addition, MELNs decreased the oxidative stress levels in liver tissue and had good biocompatibility. In vitro experiments verified that MELNs improved the viability of glucosamine (GlcN) induced insulin-resistant hepatocytes. Furthermore, this study also revealed that MELNs upregulated GLUT4 & Nrf2 and down-regulated GSK-3β via activating the PI3K/Akt signaling pathway, promoting the production of antioxidant enzymes, such as HO-1 and SOD, to reduce oxidative stress.

CONCLUSION

MELNs mitigated the progression of type 2 diabetes in HFD/STZ mouse model. The underlying molecular mechanism is related to PI3K/Akt/GLUT4/GSK-3β signaling pathway.

摘要

背景

2 型糖尿病(T2DM)是一种以高血糖和胰岛素抵抗为特征的慢性代谢性疾病。绿豆芽传统上被认为是一种“民间”降血糖食物,其药理作用和潜在机制值得进一步研究。

目的

本研究旨在探讨绿豆芽外泌体样纳米颗粒(MELNs)的抗糖尿病作用,并探讨相关的分子机制。

结果

MELNs 采用差速离心-聚乙二醇(PEG)法分离,PAGE 凝胶电泳、琼脂糖凝胶电泳、薄层层析(TLC)和透射电子显微镜(TEM)鉴定 MELNs。在高脂饮食/链脲佐菌素(HFD/STZ)小鼠模型中,MELNs 通过增加口服葡萄糖耐量试验(OGTT)和胰岛素耐量试验(ITT)结果、降低空腹血糖水平以及降低血清甘油三酯(TG)和总胆固醇(TC),改善了 T2DM 的进展。组织病理学检查表明,MELNs 减少了肝细胞的炎症浸润,放大了胰岛 B 细胞的面积。此外,MELNs 降低了肝组织的氧化应激水平,具有良好的生物相容性。体外实验验证了 MELNs 可改善氨基葡萄糖(GlcN)诱导的胰岛素抵抗肝细胞的活力。此外,本研究还表明,MELNs 通过激活 PI3K/Akt 信号通路,上调 GLUT4 和 Nrf2,下调 GSK-3β,促进抗氧化酶如 HO-1 和 SOD 的产生,从而减轻氧化应激,从而改善 HFD/STZ 小鼠模型中 2 型糖尿病的进展。

结论

MELNs 减轻了 HFD/STZ 小鼠模型中 2 型糖尿病的进展。其潜在的分子机制与 PI3K/Akt/GLUT4/GSK-3β 信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f173/10536756/219ff518ceaf/12951_2023_2120_Fig1_HTML.jpg

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