首页|Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes

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

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Insulin 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-a 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.

type 2 diabetes mellitusinsulin resistancehyperglycemia injurymesenchymal stem cellsexosome

Mei-ting CHEN、Yi-ting ZHAO、Li-yuan ZHOU、Ming LI、Qian ZHANG、Qin HAN、Xin-hua XIAO

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Department of Endocrinology,Key Laboratory of Endocrinology,Ministry of Health,Peking Union Medical College Hospital,Diabetes Research Center of Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100730,China

Department of Medical Oncology,Sun Yat-sen University Cancer Center,State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine,Guangzhou 510060,China

Department of PET-CT Center,Cancer Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100021,China

Center of Excellence in Tissue Engineering,Key Laboratory of Beijing,Institute of Basic Medical Sciences and School of Basic Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100730,China

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This work was supported by the grants from National Key Research and Development Program of ChinaNational Key R&D Program of Chinaand National Natural Science Foundation of Chinaand National Natural Science Foundation of Chinaand National Natural Science Foundation of China

2016YFA01010022017YFC1309603Nos.811707368157071581870579

2021

10.1007/s11596-021-2323-4

当代医学科学(英文)
同济医科大学

当代医学科学(英文)

SCI
ISSN：2096-5230
年,卷(期)：2021.41(1)
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