Badal, Simone; Brown, Paul D.; Ragoobirsingh, Dalip
Author Affiliation, Ana.
Department of Basic Medical Sciences
In Vitro Studies on the Effect of Nitric Oxide on IRS-1 Phosphorylation in Signal Transduction [Abstract]
West Indian Medical Journal
Date of Publication
Objective: Phosphorylation of th einsulin receptor substrate-1 (IRS-1) is critical for the insulin-mediated signal transduction pathways, which result in glucose uptake into insulin-sensitive tissues. This research was designed to investigate the effect of nitric oxide (NO) donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitroso-glutathione (GSNO) on the phosphorylation of IRS-1 in skeletal muscle. Method: Skeletal muscle tissue extracted from 6-8 week-old Sprague-Dawley rats was incubated with SNAP and GSNO (25 and 50 ng/ml), in the presence or absence of glucose (25 mM) and insulin (100 and 1000 nM). Nitric oxide (NO) released from drugs was determined as nitrite using the Greiss test and IRS-1 phosphorylation was meaured using a specific dot blot analysis. Conclusion: The study confirmed the effect of NO in signal transduction as its presence caused a significant decrease in IRS-1 phosphorylation in skeletal muscle cells. This suggests that NO is a potent inhibitor of insulin-mediated signal transduction and may be involved in the pathogenesis of diabetes mellitus.....