Effects Of Resistin On Glucose Uptake In Rat Skeletal Muscles And Its Mechanisms

Aim: To assess the effects and mechanisms of resistin on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells. Method: (1) Resistin-expressing vectors and empty vectors were transfected into 293-T cells; 24h later, cultured supernatant were harvested followed by Western blotting identification and ELISA quatitation. (2) Rat myoblasts (L6) were cultured and differentiated into myotubes followed by stimulation with "Single 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). (3) Liquid scintillation counting (LSC) was used to quantitate [³H] 2-deoxyglucose uptake. (4) The translocation of insulin-sensitive glucose transporters GLUT4, synaptosomal-associated protein 23 (SNAP23) and GLUT protein content, as well as the tyrosine phosphorylation status and protein content of insulin receptor substrate 1 (IRS-1), were assessed at 2h by Western blotting. Results: (1) Treatment of L6 myotubes with resistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impaired insulin-stimulated GLUT4 translocation. (3) While SNAP23 protein content was decreased, no effects were noted in GLUT4 or GLUT1 protein content. (4) Resistin also diminished insulin-stimulated IRS-1 tyrosine phosphorylation (IRS-1^Tyr612) levels without affecting its protein content. (5) The effects of recombinant resistin from 293-T cells transfected with resistin-expressing vectors were greater than that of single resistin treatment. Conclusion: Resistin regulated IRS-1 function and decreased GLUT4 translocation and glucose uptake in response to insulin. The down-regulated expression of SNAP23 may have been partly attributed 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.