title: Isoorientin reverts TNF-α-induced insulin resistance in adipocytes activating the insulin signaling pathway.
abstract: Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.
authors.affiliation: Instituto Potosino de Investigación Científica y Tecnológica, Molecular Biology Division, San Luis Potosí, México.
authors.forename: Angel Josabad
authors.initials: AJ
authors.lastname: Alonso-Castro
authors.forename: Rocio
authors.initials: R
authors.lastname: Zapata-Bustos
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Gómez-Espinoza
authors.forename: Luis A
authors.initials: LA
authors.lastname: Salazar-Olivo
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D014409:Tumor Necrosis Factor-alpha; D003847:Deoxyglucose; C057912:homoorientin; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; D047311:Luteolin