PMID- 33582911 OWN - NLM STAT- MEDLINE DCOM- 20211006 LR - 20211006 IS - 2523-899X (Electronic) IS - 2523-899X (Linking) VI - 41 IP - 1 DP - 2021 Feb TI - Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Insulin Sensitivity in Insulin Resistant Human Adipocytes. PG - 87-93 LID - 10.1007/s11596-021-2323-4 [doi] AB - 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-alpha 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. FAU - Chen, Mei-Ting AU - Chen MT AD - 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. AD - 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. FAU - Zhao, Yi-Ting AU - Zhao YT AD - Department of PET-CT Center, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China. FAU - Zhou, Li-Yuan AU - Zhou LY AD - 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. FAU - Li, Ming AU - Li M AD - 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. FAU - Zhang, Qian AU - Zhang Q AD - 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. FAU - Han, Qin AU - Han Q AD - 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. FAU - Xiao, Xin-Hua AU - Xiao XH AD - 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. xiaoxh2014@vip.163.com. LA - eng PT - Journal Article DEP - 20210213 PL - China TA - Curr Med Sci JT - Current medical science JID - 101729993 RN - 0 (Insulin) RN - 0 (Leptin) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.5.1.- (SIRT1 protein, human) RN - EC 3.5.1.- (Sirtuin 1) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adipocytes/cytology/*metabolism MH - Cell Differentiation MH - Cells, Cultured MH - Exosomes/*metabolism MH - Glucose/metabolism MH - Humans MH - Insulin/metabolism MH - *Insulin Resistance MH - Leptin/metabolism MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Sirtuin 1/metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Umbilical Cord/cytology OTO - NOTNLM OT - exosome OT - hyperglycemia injury OT - insulin resistance OT - mesenchymal stem cells OT - type 2 diabetes mellitus EDAT- 2021/02/15 06:00 MHDA- 2021/10/07 06:00 CRDT- 2021/02/14 20:38 PHST- 2019/10/07 00:00 [received] PHST- 2020/11/19 00:00 [accepted] PHST- 2021/02/14 20:38 [entrez] PHST- 2021/02/15 06:00 [pubmed] PHST- 2021/10/07 06:00 [medline] AID - 10.1007/s11596-021-2323-4 [pii] AID - 10.1007/s11596-021-2323-4 [doi] PST - ppublish SO - Curr Med Sci. 2021 Feb;41(1):87-93. doi: 10.1007/s11596-021-2323-4. Epub 2021 Feb 13.