PMID- 37759297 OWN - NLM STAT- MEDLINE DCOM- 20230929 LR - 20231121 IS - 1477-3155 (Electronic) IS - 1477-3155 (Linking) VI - 21 IP - 1 DP - 2023 Sep 28 TI - Natural exosomes-like nanoparticles in mung bean sprouts possesses anti-diabetic effects via activation of PI3K/Akt/GLUT4/GSK-3beta signaling pathway. PG - 349 LID - 10.1186/s12951-023-02120-w [doi] LID - 349 AB - 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-3beta 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-3beta signaling pathway. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - He, Chengxun AU - He C AD - 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. FAU - Wang, Ke AU - Wang K AD - Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China. FAU - Xia, Jun AU - Xia J AD - 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. FAU - Qian, Die AU - Qian D AD - 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. FAU - Guo, Juan AU - Guo J AD - 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. FAU - Zhong, Lian AU - Zhong L AD - 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. FAU - Tang, Dandan AU - Tang D AD - 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. FAU - Chen, Xiuping AU - Chen X AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China. FAU - Peng, Wei AU - Peng W AD - 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. pengwei@cdutcm.edu.cn. FAU - Chen, Yunhui AU - Chen Y AD - 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. chenyunhui@cdutcm.edu.cn. FAU - Tang, Yong AU - Tang Y AD - 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. tangyong@cdutcm.edu.cn. LA - eng GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ GR - 2021MS464/Sichuan Provincial Administration of Traditional Chinese Medicine/ PT - Journal Article DEP - 20230928 PL - England TA - J Nanobiotechnology JT - Journal of nanobiotechnology JID - 101152208 RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - 0 (Insulin) SB - IM MH - Animals MH - Mice MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycogen Synthase Kinase 3 beta MH - Phosphatidylinositol 3-Kinases MH - Proto-Oncogene Proteins c-akt MH - *Vigna MH - *Exosomes MH - Insulin MH - *Nanoparticles MH - Disease Models, Animal MH - Signal Transduction PMC - PMC10536756 OTO - NOTNLM OT - Exosome-like nanoparticles OT - Mung bean sprouts OT - Oxidative stress OT - Type 2 diabetes Mellitus COIS- The authors declare no competing interests. EDAT- 2023/09/28 00:42 MHDA- 2023/09/29 06:44 PMCR- 2023/09/28 CRDT- 2023/09/27 23:51 PHST- 2023/07/18 00:00 [received] PHST- 2023/09/20 00:00 [accepted] PHST- 2023/09/29 06:44 [medline] PHST- 2023/09/28 00:42 [pubmed] PHST- 2023/09/27 23:51 [entrez] PHST- 2023/09/28 00:00 [pmc-release] AID - 10.1186/s12951-023-02120-w [pii] AID - 2120 [pii] AID - 10.1186/s12951-023-02120-w [doi] PST - epublish SO - J Nanobiotechnology. 2023 Sep 28;21(1):349. doi: 10.1186/s12951-023-02120-w.