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
- 14 January 2008
- journal article
- Published by Wiley in Journal Of Physiology-London
- Vol. 586 (2), 659-671
- https://doi.org/10.1113/jphysiol.2007.142414
Abstract
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 beta (IR beta), 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 IR beta, 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.This publication has 50 references indexed in Scilit:
- Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid–induced insulin resistanceJCI Insight, 2007
- Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistanceJCI Insight, 2007
- Reversal of diet‐induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS‐1 serine phosphorylationJournal Of Physiology-London, 2006
- TLR4 links innate immunity and fatty acid–induced insulin resistanceJCI Insight, 2006
- Targeted disruption of iNOS prevents LPS-induced S-nitrosation of IRβ/IRS-1 and Akt and insulin resistance in muscle of miceAmerican Journal of Physiology-Endocrinology and Metabolism, 2006
- Inhibition of Inducible Nitric-oxide Synthase by Activators of AMP-activated Protein KinaseOnline Journal of Public Health Informatics, 2004
- A central role for JNK in obesity and insulin resistanceNature, 2002
- Direct Activation of the Olfactory Cyclic Nucleotide–Gated Channel through Modification of Sulfhydryl Groups by NO CompoundsNeuron, 1996
- Duration of Improved Muscle Glucose Uptake After Acute Exercise in Obese Zucker RatsObesity Research, 1993
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970