Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle

摘要

Background:Evidence demonstrates that exogenously administered nitric oxide(NO)can induce insulin resistance in skeletal muscle.We have investigated the modulatory effects of two NO donors,S-nitroso-N-acetyl-D,L-penicillamine(SNAP)and S-nitrosoglutathione(GSNO)on the early events in insulin signaling in rat skeletal myocytes. Results:Skeletal muscle cells from 6-8 week old Sprague-Dawley rats were treated with SNAP or GSNO(25 ng/ml)in the presence or absence of glucose(25 mM)and insulin(100 nM).Cellular insulin receptor-βlevels and tyrosine phosphorylation in IRS-1 were significantly reduced,while serine phosphorylation in IRS-1 was significantly increased in these cells,when compared to the insulin-stimulated control.Reversal to near normal levels was achieved using the NO scavenger,2- (4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide(carboxy-PTIO). Conclusion:These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.