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

Exosomes are nano-sized extracellular vesicles (EVs) that show great promise in tissue regeneration and injury repair as mesenchymal stem cell (MSC). MSC has been showed 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 therapeutic effect on type 2 DM (T2DM). We established a rat model of T2DM using high-fat diet (HFD) and streptozotocin (STZ). We found that the intravenous injection of hucMSC-ex reduced blood glucose level as 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 insulin receptor substrate1 (IRS-1) and protein kinase B in T2DM, promoted expression and membrane translocation of glucose transporter 4 (GLUT4) in muscle and increased storage of glycogen in 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 through reversing peripheral insulin resistance and relieving β-cell destruction which provide an alternative approach for T2DM treatment.