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Acute physical exercise reverses S ‐nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet‐induced obese Wistar rats
Author(s) -
Pauli José R.,
Ropelle Eduardo R.,
Cintra Dennys E.,
CarvalhoFilho Marco A.,
Moraes Juliana C.,
De Souza Cláudio T.,
Velloso Lício A.,
Carvalheira José B. C.,
Saad Mario J. A.
Publication year - 2008
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.142414
Subject(s) - irs1 , insulin receptor , medicine , endocrinology , insulin , insulin resistance , protein kinase b , insulin receptor substrate , nitric oxide synthase , nitric oxide , chemistry , signal transduction , biology , biochemistry
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‐ N 6 ‐(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.