Abstract
BackgroundGlobally, 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.MethodsIn 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.ResultsThe 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.ConclusionsThese 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.
Highlights
Diabetes mellitus is a life-long metabolic disease with high morbidity and mortality rates, and DM reduces the patients’ quality of life due to acute and chronic complications [1, 2]
Insulin can activate negative regulators of insulin signal transduction to inhibit the signal pathway in the critical nodes of insulin receptor-insulin receptor substrate (IRS)/Akt
Therapeutic effects of transplanted HUC-MSCs in db/db mice To evaluate the potential capacity of HUC-MSCs and the effect of administration route, FBG, weight, and survival rates were assessed
Summary
Diabetes mellitus is a life-long metabolic disease with high morbidity and mortality rates, and DM reduces the patients’ quality of life due to acute and chronic complications [1, 2]. Dysregulation of the insulin signaling cascade results in the development of IR [7], which has important consequences on the regulation of glucose and lipid metabolism. Insulin can activate negative regulators of insulin signal transduction to inhibit the signal pathway in the critical nodes of insulin receptor-IRS/Akt. controlling insulin signal transduction tightly is an important step to avoid severe disorder of metabolism and proliferation. Dysregulation of negative regulators in insulin signal transduction can induce the development of IR, correlated with chronic hyperactivation. Relative studies reported that level of PTEN increased in type 1 diabetic mice induced by the aortas of streptozotocin [11] and skeletal muscles of T2DM mice [12, 13]. More effective methods are required to improve insulin resistance
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