title: Genipin stimulates glucose transport in C2C12 myotubes via an IRS-1 and calcium-dependent mechanism.
abstract: Genipin, a compound derived from Gardenia jasminoides Ellis fruits, has been used over the years in traditional Chinese medicine to treat symptoms of type 2 diabetes. However, the molecular basis for its antidiabetic effect has not been fully revealed. In this study, we investigated the effects of genipin on glucose uptake and signaling pathways in C(2)C(12) myotubes. Our study demonstrates that genipin stimulated glucose uptake in a time- and dose-dependent manner. The maximal effect was achieved at 2 h with a concentration of 10 μM. In myotubes, genipin promoted glucose transporter 4 (GLUT4) translocation to the cell surface, which was observed by analyzing their distribution in subcellular membrane fraction, and increased the phosphorylation of insulin receptor substrate-1 (IRS-1), AKT, and GSK3β. Meanwhile, genipin increased ATP levels, closed K(ATP) channels, and then increased the concentration of calcium in the cytoplasm in C(2)C(12) myotubes. Genipin-stimulated glucose uptake could be blocked by both the PI3-K inhibitor wortmannin and calcium chelator EGTA. Moreover, genipin increases the level of reactive oxygen species and ATP in C(2)C(12) myotubes. These results suggest that genipin activates IRS-1, PI3-K, and downstream signaling pathway and increases concentrations of calcium, resulting in GLUT4 translocation and glucose uptake increase in C(2)C(12) myotubes.
authors.affiliation: Shanghai Key Laboratory of Endocrine Tumor, Shanghai Jiao-Tong University School of Medicine, Shanghai Institute of Endocrinology and Metabolism, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Rui-Jin Hospital, 197 Rui-Jin 2nd Road, Shanghai 200025, People's Republic of China.
authors.forename: Chan-Juan
authors.initials: CJ
authors.lastname: Ma
authors.forename: Ai-Fang
authors.initials: AF
authors.lastname: Nie
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Zhi-Guo
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Du
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D039823:Iridoids / Q000494:pharmacology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D039823:Iridoids; C526295:Irs1 protein, mouse; D017382:Reactive Oxygen Species; C007834:genipin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D002118:Calcium