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 (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.