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ACS Nano. 2018 Aug 28;12(8):7613-7628. doi: 10.1021/acsnano.7b07643. Epub 2018 Aug 7.

Human Mesenchymal Stem Cell Derived Exosomes Alleviate Type 2 Diabetes Mellitus by Reversing Peripheral Insulin Resistance and Relieving β-Cell Destruction.

Author information

1
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine , Jiangsu University , Zhenjiang , Jiangsu 212013 , China.
2
Department of Clinical Laboratory , The Affiliated Yixing Hospital of Jiangsu University , Yixing , Jiangsu 214200 , China.

Abstract

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 translocation of glucose transporter 4 in muscle, and increased storage of glycogen in the liver to maintain glucose homeostasis. HucMSC-ex inhibited STZ-induced β-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 β-cell destruction, providing an alternative approach for T2DM treatment.

KEYWORDS:

exosomes; glucose metabolism; insulin sensitivity; mesenchymal stem cell; type 2 diabetes mellitus

PMID:
30052036
DOI:
10.1021/acsnano.7b07643
[Indexed for MEDLINE]

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