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Targeted Disruption of Inducible Nitric Oxide Synthase Protects Against Aging, S -Nitrosation, and Insulin Resistance in Muscle of Male Mice

2012; American Diabetes Association; Volume: 62; Issue: 2 Linguagem: Inglês

10.2337/db12-0339

1939-327X

Eduardo R. Ropelle, José Rodrigo Pauli, Dennys E. Cintra, Adelino Sánchez Ramos da Silva, Cláudio Teodoro de Souza, Dioze Guadagnini, Bruno M. Carvalho, Andréa M. Caricilli, Carlos K. Katashima, Carvalho Filho, Sandro Massao Hirabara, Rui Curi, Lı́cio A. Velloso, Mário J.A. Saad, José Barreto Campello Carvalheira,

Adipose Tissue and Metabolism

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.