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Publication Type
Journal Article
Author, Analytic
Badal, S; Brown, Paul D; Ragoobirsingh, Dalip
Author Affiliation, Ana.
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Article Title
Exogenous nitric oxide inhibits IRS-1 expression in rat hepatocytes and skeletal myocytes
Medium Designator
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Connective Phrase
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Journal Title
Journal of Biomedical Sciences
Translated Title
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Reprint Status
Refereed
Date of Publication
2006
Volume ID
13
Issue ID
4
Page(s)
561-568
Language
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Connective Phrase
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Location/URL
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ISSN
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Notes
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Abstract
Accumulative evidence has supported the role of nitric oxide (NO) in a variety of normal physiological functions as well as many pathological conditions. In this study, we examined the possible diabetogenicity of NO by measuring the expression of the insulin receptor substrate (IRS)-1 in rat hepatocytes and skeletal myocytes. IRS-1 is important in the insulin-mediated signal transduction pathway in both liver and skeletal muscle. Exogenous NO donated by S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) resulted in significant reduction in levels of IRS-1 in both cells, when compared to the insulin-stimulated control (p<0.001). 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). SNAP was the more potent drug, and the skeletal myocytes were the more sensitive cells to the inhibitory effects of NO released from the drugs. These results provide further evidence that exogenous NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.....
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