scholarly journals Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes

2021 ◽  
Vol 41 (1) ◽  
pp. 87-93
Author(s):  
Mei-ting Chen ◽  
Yi-ting Zhao ◽  
Li-yuan Zhou ◽  
Ming Li ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Umbilical Cord ◽  
Sirtuin 1 ◽  
Human Umbilical Cord ◽  
Human Adipocytes ◽  
Insulin Resistant

SummaryInsulin resistance is an essential characteristic of type 2 diabetes mellitus (T2DM), which can be induced by glucotoxicity and adipose chronic inflammation. Mesenchymal stem cells (MSCs) and their exosomes were reported to ameliorate T2DM and its complications by their immunoregulatory and healing abilities. Exosomes derived from MSCs contain abundant molecules to mediate crosstalk between cells and mimic biological function of MSCs. But the role of exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) in insulin resistance of human adipocytes is unclear. In this study, exosomes were harvested from the conditioned medium of hUC-MSCs and added to insulin-resistant adipocytes. Insulin-stimulated glucose uptake was measured by glucose oxidase/peroxidase assay. The signal pathway involved in exosome-treated adipocytes was detected by RT-PCR and Western blotting. The biological characteristics and function were compared between hUC-MSCs and human adipose-derived mesenchymal stem cells (hAMSCs). The results showed that hAMSCs had better adipogenic ability than hUC-MSCs. After induction of mature adipocytes by adipogenesis of hAMSC, the model of insulin-resistant adipocytes was successfully established by TNF-α and high glucose intervention. After exosome treatment, the insulin-stimulated glucose uptake was significantly increased. In addition, the effect of exosomes could be stabilized for at least 48 h. Furthermore, the level of leptin was significantly decreased, and the mRNA expression of sirtuin-1 and insulin receptor substrate-1 was significantly upregulated after exosome treatment. In conclusion, exosomes significantly improve insulin sensitivity in insulin-resistant human adipocytes, and the mechanism involves the regulation of adipokines.

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Fasting Blood Glucose ◽  
Mapk Signaling ◽  
Human Umbilical Cord ◽  
Multiple Drugs

Abstract Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus (T2DM). Asia is the epicenter of this global T2DM epidemic. T2DM and its complications have contributed significantly to the burden of mortality and disability worldwide. Insulin resistance (IR) is a central defect in T2DM, and although multiple drugs have been developed to ameliorate IR, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve IR.Methods: In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection (IV), intraperitoneal injection (IP) and skeletal muscle injection (IM). Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-IR effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo.Results: The results showed that HUC-MSC transplantation by IM was safer compared with IV and IP, and the survival rate reached 100% in the IM transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate IR. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway.Conclusions: These results suggest HUC-MSC transplantation by IM may be a novel therapeutic direction to prevent IR and increase insulin sensitivity.

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