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 Insulin-Mediated Signal Transduction [Abstract]
West Indian Medical Journal
Date of Publication
Objective: Phosphorylation of the insulin receptor substrate-1 (IRS-1) is important in the insulin mediated signal transduction pathway. This study investigated the effect of nitric oxide (NO) released from S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and S-nitrosoglutathione (GSNO) on the phosphorylation of IRS-1 in skeletal muscle cells. Design and Methods: Skeletal muscle tissue extracted from 6-8 weeks old Sprague-Dawley rats was subjected to collagenase digestion and isolated cells were exposed to the druhs 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 released from drugs was determined as NO2 - using the Greiss reagent and IRS-1 phosphorylation was measured using a specific dot blot analysis. Conclusion: The study confirms the effect of NO on signal transduction as its presence caused a significant decrease in IRS-1 phoshorylation in skeletal muscle cells. This suggests that NO is a potent inhibitor of insulin mediated signal transduction and possibly plays a role in the pathogenesis of diabetes mellitus.....