Aim:To assess the effects and mechanisms of the action of resistin on basal andinsulin-stimulated glucose uptake in rat skeletal muscle cells.Methods:Rat myo-blasts(L6)were cultured and differentiated into myotubes followed by stimula-tion with single commercial resistin(130 ng/mL,0-24 h)or cultured supernatantfrom 293-T cells transfected with resistin-expressing vectors(130 ng/mL,0-24 h).Liquid scintillation counting was used to quantitate[~3H]2-deoxyglucose uptake.The translocation of insulin-sensitive glucose transporters GLUT4 and GLUT1,synaptosomal-associated protein 23(SNAP23)and GLUT protein content,as wellas the tyrosine phosphorylation status and protein content of insulin receptorsubstrate(IRS)-1,were assessed by Western blotting.Results:Treatment of L6myotubes with single resistin or cultured supernatant containing recombinantresistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impairedinsulin-stimulated GLUT4 translocation.While SNAP23 protein content wasdecreased,no effects were noted in GLUT4 or GLUT1 protein content.Resistinalso diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels withoutaffecting its protein content.The effects of recombinant resistin from 293-T cellstransfected with resistin-expressing vectors were greater than that of single resistintreatment.Conclusion:Resistin regulated IRS-1 function and decreased GLUT4translocation and glucose uptake in response to insulin.The downregulatedexpression of SNAP23 may have been partly attributed to the decrease of glucoseuptake by resistin treatment.These observations highlight the potential role ofresistin in the pathophysiology of type 2 diabetes related to obesity. Aim: To assess the effects and mechanisms of the action of resistin on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells. Methods: Rat myo-blasts (L6) were cultured and differentiated into myotubes followed by stimula tion with single commercial resistin (130 ng / mL, 0-24 h) or cultured supernatant from 293-T cells transfected with resistin-expressing vectors (130 ng / mL, 0-24 h). Liquid scintillation counting was used to quantitate [~ 3H] uptake. The translocation of insulin-sensitive glucose transporters GLUT4 and GLUT1, synaptosomal-associated protein 23 (SNAP23) and GLUT protein content, as wellas the tyrosine phosphorylation status and protein content of insulin receptor substrate (IRS) -1, were assessed by Western blotting .Results: Treatment of L6 myotubes with single resistin or cultured supernatant containing recombinantresistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impaired insulin-stimulated GLUT4 translocation. Whilst SNAP23 protein content was decreased, no effects were noted in GLUT4 or GLUT1 protein content. Resistinalso diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels without affecting protein content. The effects of recombinant resistin from 293-T cellstransfected with resistin-expressing vectors were greater than that of single resistintreatment.Conclusion: Resistin regulated IRS-1 function and decreased GLUT4 transition and glucose uptake in response to insulin. The downregulate expression of SNAP23 may have been attributable to the decrease of glucose uptake by resistin treatment. these observations highlight the potential role of resistin in the pathophysiology of type 2 diabetes related to obesity.