期刊
ACS NANO
卷 12, 期 8, 页码 7613-7628出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.7b07643
关键词
exosomes; mesenchymal stem cell; type 2 diabetes mellitus; insulin sensitivity; glucose metabolism
类别
资金
- National Natural Science Foundation of China [81572075, 81670549, 81670502]
- Natural Science Foundation of Jiangsu Province [BE2016717, BE2015667]
- Innovation Project for Graduate Student Research of Jiangsu Province [KYZZ16_0342]
- opening project of the Key Laboratory of Embryo Molecular Biology, Ministry of Health of China
- Shanghai Key Laboratory of Embryo and Reproduction Engineering [KF201601]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
Exosomes are nanosized extracellular vesicles (EVs) that show great promise in tissue regeneration and injury repair as mesenchymal stem cell (MSC). MSC has been shown to alleviate diabetes mellitus (DM) in both animal models and clinical trials. In this study, we aimed to investigate whether exosomes from human umbilical cord MSC (hucMSC-ex) have a therapeutic effect on type 2 DM (T2DM). We established a rat model of T2DM using a high-fat diet and streptozotocin (STZ). We found that the intravenous injection of hucMSC-ex reduced blood glucose levels as a main paracrine approach of MSC. HucMSC-ex partially reversed insulin resistance in T2DM indirectly to accelerate glucose metabolism. HucMSC-ex restored the phosphorylation (tyrosine site) of the insulin receptor substrate 1 and protein kinase B in T2DM, promoted expression and membrane trans location of glucose transporter 4 in muscle, and increased storage of glycogen in the liver to maintain glucose homeostasis. HucMSC-ex inhibited STZ-induced beta-cell apoptosis to restore the insulin-secreting function of T2DM. Taken together, exosomes from hucMSC can alleviate T2DM by reversing peripheral insulin resistance and relieving beta-cell destruction, providing an alternative approach for T2DM treatment.
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