Activation of Insulin Signaling in Adipocytes and Myotubes by Sarcopoterium Spinosum Extract

Sarcopoterium spinosum (S. spinosum) is a medicinal plant, traditionally used as an antidiabetic remedy. Previous studies demonstrated its beneficial properties in the treatment of insulin resistance. The aim of this study was to further clarify the effect of S. spinosum extract (SSE) on insulin signaling. Phosphoproteomic analysis, performed in 3T3-L1 adipocytes treated with SSE, revealed the activation of insulin receptor pathways. SSE increased Glut4-facilitated glucose uptake in adipocytes, with an additive effect between SSE and insulin. While the maximal effect of insulin on glucose uptake was found at days 15-16 of differentiation, SSE-induced glucose uptake was found at an earlier stage of differentiation. Inhibition of PI3K and Akt blocked SSE-dependent glucose uptake. Western blot analysis, performed on 3T3-L1 adipocytes and L6 myotubes, showed that in contrast to insulin action, Akt was only marginally phosphorylated by SSE. Furthermore, GSK3β and PRAS40 phosphorylation as well as glucose uptake were increased by the extract. SSE also induced the phosphorylation of ERK similar to insulin. In conclusion, SSE activates insulin signaling, although the upstream event mediating its effects should be further clarified. Identifying the active molecules in SSE may lead to the development of new agents for the treatment of insulin resistance.