1. Targeted disruption of inducible nitric oxide synthase protects against aging, S-nitrosation, and insulin resistance in muscle of male mice
- Author
-
Ropelle, Eduardo R., Pauli, Jose R., Cintra, Dennys E., da Silva, Adelino S., De Souza, Claudio T., Guadagnini, Dioze, Carvalho, Bruno M., Caricilli, Andrea M., Katashima, Carlos K., Carvalho-Filho, Marco A., Hirabara, Sandro, Curi, Rui, Velloso, Licio A., Saad, Mario J.A., and Carvalheira, Jose B.C.
- Subjects
Insulin resistance -- Risk factors -- Genetic aspects -- Research ,Nitric oxide -- Physiological aspects -- Research ,Muscles -- Physiological aspects -- Genetic aspects -- Research ,Health - Abstract
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., In recent decades, S-nitrosation, the reaction of nitric oxide (NO) with cysteine residues in proteins to form S-nitrosothiol adducts, in addition to phosphorylation, acetylation, and ubiquitination, has become one of [...]
- Published
- 2013
- Full Text
- View/download PDF