Enhancing myogenesis has been identified as a possible target to improve insulin sensitivity and protect against metabolic diseases. Catalpol, an iridoid glycoside, has been shown to exert a hypoglycaemic effect by improvement of insulin sensitivity; however, the underlying mechanism remains unknown. In this study, we tested whether catalpol has the potential to improve insulin sensitivity by augmenting myogenesis.Main methods:
We examined the hypoglycaemic mechanism of catalpol in db/db mice and C2C12 cells. db/db mice were treated with catalpol (200 mg/kg) for 8 consecutive weeks. Serum analysis, skeletal muscle performance and histology, and gene and protein expression were performed. In vitro glucose uptake, gene and protein expression were determined, and small interfering RNA was used to identify the underlying hypoglycaemic mechanism of catalpol.Key findings:
In this study, we tested whether catalpol has the potential to improve skeletal insulin sensitivity by augmenting myogenesis, in which we found that, catalpol treatment in db/db mice lowered blood glucose and improved insulin sensitivity via activation of phosphatidylinositol-3-Kinase (PI3K)/protein kinase B (AKT) pathway. Moreover, catalpol-treated mice exhibited enhanced myogenesis, as evidenced by increased myogenic differentiation (MyoD), myogenin (MyoG) and myosin heavy chain (MHC) expressions. The in vitro experimental results showed that both catalpol and metformin enhanced glucose uptake via activation of PI3K/AKT pathway. However, unlike metformin, the PI3K/AKT pathway activation by catalpol was dependent on enhanced MyoD/MyoG-mediated myogenesis.Significance:
Improvement of insulin sensitivity by enhancing MyoD/MyoG-mediated myogenesis may constitute a new therapeutic approach for treating type 2 diabetes.