期刊
DIABETES
卷 62, 期 2, 页码 466-470出版社
AMER DIABETES ASSOC
DOI: 10.2337/db12-0339
关键词
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资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
- Conselho Nacional de desenvolvimento cientifico e tecnologico
Accumulating evidence has demonstrated that S-nitrosation of proteins plays a critical role in several human diseases. Here, we explored the role of inducible nitric oxide synthase (iNOS) in the S-nitrosation of proteins involved in the early steps of the insulin-signaling pathway and insulin resistance in the skeletal muscle of aged mice. Aging increased iNOS expression and S-nitrosation of major proteins involved in insulin signaling, thereby reducing insulin sensitivity in skeletal muscle. Conversely, aged iNOS-null mice were protected from S-nitrosation-induced insulin resistance. Moreover, pharmacological treatment with an iNOS inhibitor and acute exercise reduced iNOS-induced S-nitrosation and increased insulin sensitivity in the muscle of aged animals. These findings indicate that the insulin resistance observed in aged mice is mainly mediated through the S-nitrosation of the insulin-signaling pathway. Diabetes 62:466-470, 2013
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