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. 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. 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. 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.

中文翻译：

---

人脐带间充质干细胞通过 PTEN 介导的 db/db 小鼠骨骼肌中 PI3K/Akt 和 Erk/MAPKs 信号通路之间的串扰改善胰岛素抵抗。

在全球范围内，每 11 名成年人中就有 1 名患有糖尿病，其中 90% 的病例为 2 型糖尿病。胰岛素抵抗是 2 型糖尿病的核心缺陷，尽管已经开发了多种药物来改善胰岛素抵抗，但其局限性和伴随的副作用不容忽视。因此，需要更有效的方法来改善胰岛素抵抗。在目前的研究中，db/m 和 db/db 小鼠通过尾静脉注射、腹腔注射和骨骼肌注射注射人脐带间充质干细胞 (HUC-MSCs)。监测体重、空腹血糖和存活率。此外，在 db/db 小鼠体内研究了移植的 HUC-MSCs 的抗胰岛素抵抗作用和潜在机制。结果表明，与尾静脉注射和腹腔注射相比，骨骼肌注射HUC-MSC移植更安全，骨骼肌注射移植小鼠的存活率达到100%。HUC-MSCs可以稳定骨骼肌组织的定位和分化，显着改善胰岛素抵抗。潜在的调节机制与炎症的下调有关，通过 PTEN 调节 PI3K/Akt 和 ERK/MAPK 信号通路之间的平衡，但与 IGF-1/IGF-1R 信号通路无关。这些结果表明，HUC-MSC移植可能是预防胰岛素抵抗和增加胰岛素敏感性的新治疗方向，骨骼肌注射是最安全、最有效的方法。