title: 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.
authors.affiliation: Department of Internal Medicine, The 95th Hospital of Chinese People's Liberation Army, Putian, Fujian 351100, P.R. China.
authors.forename: Rongfeng
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Internal Medicine, The 95th Hospital of Chinese People's Liberation Army, Putian, Fujian 351100, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Internal Medicine, The 95th Hospital of Chinese People's Liberation Army, Putian, Fujian 351100, P.R. China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, The 95th Hospital of Chinese People's Liberation Army, Putian, Fujian 351100, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
authors.affiliation: Department of Internal Medicine, The 95th Hospital of Chinese People's Liberation Army, Putian, Fujian 351100, P.R. China.
authors.forename: Shengli
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000819:agonists* / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha / Q000235:genetics / Q000378:metabolism; D019308:Palmitic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; C526295:Irs1 protein, mouse; D012503:Saponins; C495693:Slc2a4 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D000072000:NF-KappaB Inhibitor alpha; D019308:Palmitic Acid; C052064:astragaloside A; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D005947:Glucose