Astragaloside IV facilitates glucose transport in C2C12 myotubes through the IRS1/AKT pathway and suppresses the palmitate-induced activation of the IKK/IκBα pathway

Abstract

Astragaloside IV is a monomer isolated from Astragalus membranaceus (Fisch.) Bunge, which is one of the most widely used plant-derived drugs in traditional Chinese medicine for diabetes therapy. In the present study, we aimed to examine the effects of astragaloside IV on glucose in C2C12 myotubes and the underlying molecular mechanisms responsible for these effects. Four-day differentiated C2C12 myotubes were exposed to palmitate for 16 h in order to establish a model of insulin resistance and 3H glucose uptake, using 2-Deoxy‑D‑[1,2-3H(N)]-glucose (radiolabeled 2-DG), was detected. Astragaloside IV was added 2 h prior to palmitate exposure. The translocation of glucose transporter 4 (GLUT4) was evaluated by subcellular fractionation, and the expression of insulin signaling molecules such as insulin receptor β (IRβ), insulin receptor substrate (IRS)1/protein kinase B (AKT) and inhibitory κB kinase (IKK)/inhibitor-κBα (IκBα), which are associated with insulin signal transduction, were assessed in the basal or the insulin‑stimulated state using western blot analysis or RT-PCR. We also examined the mRNA expression of monocyte chemotactic protein 1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor α (TNFα) and Toll‑like receptor 4 (TLR4). Taken together, these findings demonstrated that astragaloside IV facilitates glucose transport in C2C12 myotubes through a mechanism involving the IRS1/AKT pathway, and suppresses the palmitate-induced activation of the IKK/IκBα pathway.