PMID- 32938466 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20220531 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 11 IP - 1 DP - 2020 Sep 16 TI - 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. PG - 401 LID - 10.1186/s13287-020-01865-7 [doi] LID - 401 AB - BACKGROUND: Globally, 1 in 11 adults have diabetes mellitus, and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus, more effective methods are required to improve insulin resistance. 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, intraperitoneal injection, and skeletal muscle injection. Body weight, fasting blood glucose, and the survival rates were monitored. Furthermore, the anti-insulin resistance 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 skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. 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 may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way. FAU - Chen, Guang AU - Chen G AD - Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, No 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. AD - Department of Basic Medical Sciences, Jiamusi University, No 148 Xuefu road, Xiangyang District, Jiamusi, 154007, China. FAU - Fan, Xiao-Yan AU - Fan XY AD - Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, No 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Zheng, Xiao-Peng AU - Zheng XP AD - Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, No 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Jin, Yue-Lei AU - Jin YL AD - Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou University, No 1139 Shifu Road, Jiaojiang District, Taizhou, 318000, China. FAU - Liu, Ying AU - Liu Y AD - Jilin Tuhua Bioengineering Company Limited, Shiling Town, Tiedong District, Siping, Jilin, 136000, China. FAU - Liu, Shuang-Chun AU - Liu SC AD - Municipal Hospital Affiliated to Medical School of Taizhou University, No 381, Zhongshan east road, Jiaojiang district, Taizhou, 318000, China. dachun3065@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200916 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.1.3.67 (PTEN Phosphohydrolase) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2 MH - Humans MH - *Insulin Resistance MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - Mice MH - Muscle, Skeletal/*physiology MH - PTEN Phosphohydrolase/genetics MH - Phosphatidylinositol 3-Kinases/genetics MH - Proto-Oncogene Proteins c-akt/genetics MH - Signal Transduction MH - Umbilical Cord/cytology PMC - PMC7493876 OTO - NOTNLM OT - Db/db mice OT - Erk/MAPK OT - HUC-MSCs OT - Insulin resistant OT - PI3K/Akt OT - PTEN, crosstalk COIS- The authors declare that they have no competing interests. EDAT- 2020/09/18 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/09/16 CRDT- 2020/09/17 05:31 PHST- 2020/02/18 00:00 [received] PHST- 2020/07/30 00:00 [accepted] PHST- 2020/07/23 00:00 [revised] PHST- 2020/09/17 05:31 [entrez] PHST- 2020/09/18 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/09/16 00:00 [pmc-release] AID - 10.1186/s13287-020-01865-7 [pii] AID - 1865 [pii] AID - 10.1186/s13287-020-01865-7 [doi] PST - epublish SO - Stem Cell Res Ther. 2020 Sep 16;11(1):401. doi: 10.1186/s13287-020-01865-7.