Targeted disruption of inducible nitric oxide synthase protects against age-related s-nitrosation and insulin resistance in muscle of male mice

• Grant number: 12/18514-8
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: October 01, 2012
• End date: March 31, 2013
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Eduardo Rochete Ropelle
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil

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. (AU)