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This Article Full Text Full Text (PDF) All Versions of this Article: 586/2/659    most recent jphysiol.2007.142414v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pauli, J. R. Articles by Saad, M. J. A. Search for Related Content PubMed PubMed Citation Articles by Pauli, J. R. Articles by Saad, M. J. A. Related Collections Skeletal Muscle and Exercise

¹ Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil

Early evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance. Here, we investigated whether this insulin resistance, mediated by S-nitrosation of proteins involved in early steps of the insulin signal transduction pathway, could be reversed by acute physical exercise. Rats on a high-fat diet were subjected to swimming for two 3 h-long bouts, separated by a 45 min rest period. Two or 16 h after the exercise protocol the rats were killed and proteins from the insulin signalling pathway were analysed by immunoprecipitation and immunoblotting. We demonstrated that a high-fat diet led to an increase in the iNOS protein level and S-nitrosation of insulin receptor β (IRβ), insulin receptor substrate 1 (IRS1) and Akt. Interestingly, an acute bout of exercise reduced iNOS expression and S-nitrosation of proteins involved in the early steps of insulin action, and improved insulin sensitivity in diet-induced obesity rats. Furthermore, administration of GSNO (NO donor) prevents this improvement in insulin action and the use of an inhibitor of iNOS (L-N⁶-(1-iminoethyl)lysine; L-NIL) simulates the effects of exercise on insulin action, insulin signalling and S-nitrosation of IRβ, IRS1 and Akt. In summary, a single bout of exercise reverses insulin sensitivity in diet-induced obese rats by improving the insulin signalling pathway, in parallel with a decrease in iNOS expression and in the S-nitrosation of IR/IRS1/Akt. The decrease in iNOS protein expression in the muscle of diet-induced obese rats after an acute bout of exercise was accompanied by an increase in AMP-activated protein kinase (AMPK) activity. These results provide new insights into the mechanism by which exercise restores insulin sensitivity.

(Received 3 August 2007; accepted after revision 30 October 2007; first published online 1 November 2007)
Corresponding author M. J. A. Saad: Departamento de Clínica Médica, FCM-UNICAMP, Cidade Universitária Zeferino Vaz, Campinas, SP, Brasil. Email: msaad{at}fcm.unicamp.com.br

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