It is widely accepted that infusion of mesenchymal stem cells (MSCs) ameliorates hyperglycemia by alleviating insulin resistance in rats with type 2 diabetes mellitus (T2D). However, the detailed underlying mechanisms are not clearly defined. Mitsugumin 53 (MG53) is an E3 ligase that has recently been implicated in the aggravation of insulin resistance by promoting the ubiquitinoylation of insulin receptor substrate‑1 (IRS‑1) in skeletal muscles. It was therefore hypothesized that MG53 may be involved in MSC‑mediated therapeutic effects on insulin resistance. To test this hypothesis, in the present study, T2D rat models were induced by a high‑fat diet combined with streptozotocin administration and MSC infusion was performed four times (once every 2 weeks for 8 weeks). The therapeutic effects of MSC infusion on insulin resistance were evaluated and the effect on the expression of MG53 and insulin receptor signaling elements in skeletal muscle was also investigated by immunofluorescence staining and western blotting. The results demonstrated that MSC infusion ameliorated hyperglycemia and insulin resistance in T2D rats. Furthermore, MSC infusion inhibited MG53 elevation and reversed the decreases in glucose transporter type 4, insulin receptor, IRS‑1 and phosphorylated‑AKT levels in the skeletal muscle of T2D rats. These results indicated that MSC infusion has therapeutic effects in rats and that MG53 in skeletal muscle may be a promising novel therapeutic target protein for MSC‑mediated amelioration of insulin resistance in T2D.

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