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
Abstract 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 accompanyi...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01865-7 |
| _version_ | 1818244558930051072 |
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| author | Guang Chen Xiao-yan Fan Xiao-peng Zheng Yue-lei Jin Ying Liu Shuang-chun Liu |
| author_facet | Guang Chen Xiao-yan Fan Xiao-peng Zheng Yue-lei Jin Ying Liu Shuang-chun Liu |
| author_sort | Guang Chen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T14:18:56Z |
| format | Article |
| id | doaj.art-2a73569497784b9cbf96e178aa3d8f29 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-12T14:18:56Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-2a73569497784b9cbf96e178aa3d8f292022-12-22T00:21:50ZengBMCStem Cell Research & Therapy1757-65122020-09-0111111310.1186/s13287-020-01865-7Human 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 miceGuang Chen0Xiao-yan Fan1Xiao-peng Zheng2Yue-lei Jin3Ying Liu4Shuang-chun Liu5Department of Basic Medical Sciences, Taizhou University Hospital, Taizhou UniversityDepartment of Basic Medical Sciences, Taizhou University Hospital, Taizhou UniversityDepartment of Basic Medical Sciences, Taizhou University Hospital, Taizhou UniversityDepartment of Basic Medical Sciences, Taizhou University Hospital, Taizhou UniversityJilin Tuhua Bioengineering Company LimitedMunicipal Hospital Affiliated to Medical School of Taizhou UniversityAbstract 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.http://link.springer.com/article/10.1186/s13287-020-01865-7HUC-MSCsInsulin resistantPTEN, crosstalkPI3K/AktErk/MAPKDb/db mice |
| spellingShingle | Guang Chen Xiao-yan Fan Xiao-peng Zheng Yue-lei Jin Ying Liu Shuang-chun Liu 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 Stem Cell Research & Therapy HUC-MSCs Insulin resistant PTEN, crosstalk PI3K/Akt Erk/MAPK Db/db mice |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | HUC-MSCs Insulin resistant PTEN, crosstalk PI3K/Akt Erk/MAPK Db/db mice |
| url | http://link.springer.com/article/10.1186/s13287-020-01865-7 |
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