Aspirin attenuates insulin resistance in muscle of diet-induced obese rats by inhibiting inducible nitric oxide synthase production and S-nitrosylation of IRβ/IRS-1 and Akt Export

@article{citeulike:5811938, abstract = {Abstract Aim/hypothesis\ \ High-dose aspirin treatment improves fasting and postprandial hyperglycaemia in patients with type 2 diabetes, as well as in animal models of insulin resistance associated with obesity and sepsis. In this study, we investigated the effects of aspirin treatment on inducible nitric oxide synthase (iNOS)-mediated insulin resistance and on S-nitrosylation of insulin receptor (IR)-β, IRS-1 and protein kinase B (Akt) in the muscle of diet-induced obese rats and also in iNos (also known as Nos2)−/− mice on high fat diet. Methods\ \ Aspirin (120\ mg\ kg−1\ day−1 for 2\ days) or iNOS inhibitor (L-NIL; 80\ mg/kg body weight) were administered to diet-induced obese rats or mice and iNOS production and insulin signalling were investigated. S-nitrosylation of IRβ/IRS-1 and Akt was investigated using the biotin switch method. Results\ \ iNOS protein levels increased in the muscle of diet-induced obese rats, associated with an increase in S-nitrosylation of IRβ, IRS-1 and Akt. These alterations were reversed by aspirin treatment, in parallel with an improvement in insulin signalling and sensitivity, as measured by insulin tolerance test and glucose clamp. Conversely, while aspirin reversed the increased phosphorylation of IκB kinase β and c-Jun amino-terminal kinase, as well as IRS-1 serine phosphorylation in diet-induced obese rats and iNos −/− mice on high-fat diet, these alterations were not associated with the improvement of insulin action induced by this drug. Conclusions/interpretation\ \ Our data demonstrate that aspirin treatment not only reduces iNOS protein levels, but also S-nitrosylation of IRβ, IRS-1 and Akt. These changes are associated with improved insulin resistance and signalling, suggesting a novel mechanism of insulin sensitisation evoked by aspirin treatment.}, author = {Carvalho-Filho, M. and Ropelle, E. and Pauli, R. and Cintra, D. and Tsukumo, D. and Silveira, L. and Curi, R. and Carvalheira, J. and Velloso, L. and Saad, M.}, citeulike-article-id = {5811938}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00125-009-1498-1}, citeulike-linkout-1 = {http://www.springerlink.com/content/9136nq5241u55866}, day = {1}, doi = {10.1007/s00125-009-1498-1}, journal = {Diabetologia}, keywords = {akt, aspirin, inflammation}, month = {November}, number = {11}, pages = {2425--2434}, posted-at = {2009-10-12 00:21:48}, priority = {2}, title = {Aspirin attenuates insulin resistance in muscle of diet-induced obese rats by inhibiting inducible nitric oxide synthase production and S-nitrosylation of IRβ/IRS-1 and Akt}, url = {http://dx.doi.org/10.1007/s00125-009-1498-1}, volume = {52}, year = {2009} }

TY - JOUR ID - citeulike:5811938 L3 - citeulike-article-id:5811938 N2 - Abstract Aim/hypothesis  High-dose aspirin treatment improves fasting and postprandial hyperglycaemia in patients with type 2 diabetes, as well as in animal models of insulin resistance associated with obesity and sepsis. In this study, we investigated the effects of aspirin treatment on inducible nitric oxide synthase (iNOS)-mediated insulin resistance and on S-nitrosylation of insulin receptor (IR)-β, IRS-1 and protein kinase B (Akt) in the muscle of diet-induced obese rats and also in iNos (also known as Nos2)−/− mice on high fat diet. Methods  Aspirin (120 mg kg−1 day−1 for 2 days) or iNOS inhibitor (L-NIL; 80 mg/kg body weight) were administered to diet-induced obese rats or mice and iNOS production and insulin signalling were investigated. S-nitrosylation of IRβ/IRS-1 and Akt was investigated using the biotin switch method. Results  iNOS protein levels increased in the muscle of diet-induced obese rats, associated with an increase in S-nitrosylation of IRβ, IRS-1 and Akt. These alterations were reversed by aspirin treatment, in parallel with an improvement in insulin signalling and sensitivity, as measured by insulin tolerance test and glucose clamp. Conversely, while aspirin reversed the increased phosphorylation of IκB kinase β and c-Jun amino-terminal kinase, as well as IRS-1 serine phosphorylation in diet-induced obese rats and iNos −/− mice on high-fat diet, these alterations were not associated with the improvement of insulin action induced by this drug. Conclusions/interpretation  Our data demonstrate that aspirin treatment not only reduces iNOS protein levels, but also S-nitrosylation of IRβ, IRS-1 and Akt. These changes are associated with improved insulin resistance and signalling, suggesting a novel mechanism of insulin sensitisation evoked by aspirin treatment. IS - 11 JF - Diabetologia EP - 2434 TI - Aspirin attenuates insulin resistance in muscle of diet-induced obese rats by inhibiting inducible nitric oxide synthase production and S-nitrosylation of IRβ/IRS-1 and Akt VL - 52 SP - 2425 KW - akt KW - aspirin KW - inflammation AU - Carvalho-Filho, M AU - Ropelle, E AU - Pauli, R AU - Cintra, D AU - Tsukumo, D AU - Silveira, L AU - Curi, R AU - Carvalheira, J AU - Velloso, L AU - Saad, M PY - 2009/11/01/ UR - http://dx.doi.org/10.1007/s00125-009-1498-1 ER -