Effect of N-acetylcysteine infusion on exercise-induced modulation of insulin sensitivity and signaling pathways in human skeletal muscle

American Journal of Physiology - Endocrinology and Metabolism

Volumn 309, Issue 4, 2015, Pages E388-E397

  Trewin, Adam J ^a   Lundell, Leonidas S ^b   Perry, Ben D ^a   Patil, Kim Vikhe ^b   Chibalin, Alexander V ^b   Levinger, Itamar ^a   McQuade, Leon R ^c   Stepto, Nigel K ^a  

^a VICTORIA UNIVERSITY   (Australia)

^b KAROLINSKA INSTITUTE   (Sweden)

^c MACQUARIE UNIVERSITY   (Australia)

Author keywords

Exercise; Insulin sensitivity; Reactive oxygen species; Signaling

Indexed keywords

ACETYLCYSTEINE; INSULIN; REACTIVE OXYGEN METABOLITE;

ADULT; ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; EXERCISE; FEMALE; HUMAN; HUMAN EXPERIMENT; IMMUNOBLOTTING; INSULIN SENSITIVITY; MALE; MUSCLE BIOPSY; NORMAL HUMAN; PRIORITY JOURNAL; PROTEIN CARBONYLATION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; RANDOMIZED CONTROLLED TRIAL; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; DRUG EFFECTS; EXERCISE TEST; GLUCOSE CLAMP TECHNIQUE; INSULIN RESISTANCE; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; MUSCLE CONTRACTION; PHYSIOLOGY; YOUNG ADULT;

ACETYLCYSTEINE; ADULT; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; EXERCISE; EXERCISE TEST; FEMALE; GLUCOSE CLAMP TECHNIQUE; HUMANS; INFUSIONS, INTRAVENOUS; INSULIN; INSULIN RESISTANCE; MALE; MUSCLE CONTRACTION; MUSCLE, SKELETAL; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; YOUNG ADULT;

EID: 84939428360     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00605.2014     Document Type: Article

References (57)

1. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings B. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15: 6541, 1996.
2. Benziane B, Burton TJ, Scanlan B, Galuska D, Canny BJ, Chibalin AV, Zierath JR, Stepto NK. Divergent cell signaling after short-term intensified endurance training in human skeletal muscle. Am J Physiol Endocrinol Metab 295: E1427–E1438, 2008.
3. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3: 1014–1019, 2001.
4. Bolster DR, Crozier SJ, Kimball SR, Jefferson LS. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277: 23977–23980, 2002.
5. Brown M, Bjorksten A, Medved I, McKenna M. Pharmacokinetics of intravenous N-acetylcysteine in men at rest and during exercise. Eur J Clin Pharmacol 60: 717–723, 2004.
6. DeFronzo RA, Gunnarsson R, Björkman O, Olsson M, Wahren J. Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus. J Clin Invest 76: 149–155, 1985.
7. Deshmukh AS, Treebak JT, Long YC, Viollet B, Wojtaszewski JF, Zierath JR. Role of adenosine 5=-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling. Mol Endocrinol 22: 1105–1112, 2008.
8. Fisher-Wellman KH, Neufer PD. Linking mitochondrial bioenergetics to insulin resistance via redox biology. Trends Endocrinol Metab 23: 142–153, 2012.
9. Funai K, Schweitzer GG, Sharma N, Kanzaki M, Cartee GD. Increased AS160 phosphorylation, but not TBC1D1 phosphorylation, with increased postexercise insulin sensitivity in rat skeletal muscle. Am J Physiol Endocrinol Metab 297: E242–E251, 2009.
10. Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Viña J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 87: 142–149, 2008.
11. Gomez-Cabrera MC, Borrás C, Pallardó FV, Sastre J, Ji LL, Viña J. Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats. J Physiol 567: 113–120, 2005.
12. Goodyear L, Chang P, Sherwood D, Dufresne S, Moller D. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletal muscle. Am J Physiol Endocrinol Metab 271: E403–E408, 1996.
13. Henriksen EJ, Diamond-Stanic MK, Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radic Biol Med 51: 993–999, 2011.
14. Higashida K, Kim SH, Higuchi M, Holloszy JO, Han DH. Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab 301: E779–E784, 2011.
15. Howlett KF, Mathews A, Garnham A, Sakamoto K. The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle. Am J Physiol Endocrinol Metab 294: E401–E407, 2008.
16. Hutchison SK, Stepto NK, Harrison CL, Moran LJ, Strauss BJ, Teede HJ. Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome. J Clin Endocrinol Metab 96: E48–E56, 2011.
17. Jessen N, An D, Lihn AS, Nygren J, Hirshman MF, Thorell A, Goodyear LJ. Exercise increases TBC1D1 phosphorylation in human skeletal muscle. Am J Physiol Endocrinol Metab 301: E164–E171, 2011.
18. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685, 1970.
19. Levinger I, Jerums G, Stepto NK, Parker L, Serpiello FR, McConell GK, Anderson M, Hare DL, Byrnes E, Ebeling PR, Seeman E. The effect of acute exercise on undercarboxylated osteocalcin and insulin sensitivity in obese men. J Bone Miner Res 29: 2571–2576, 2014.
20. Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S, Bruce C, Shields BJ, Skiba B, Ooms LM. Reactive oxygen species enhance insulin sensitivity. Cell Metab 10: 260–272, 2009.
21. Luo S, Wehr NB. Protein carbonylation: avoiding pitfalls in the 2,4- dinitrophenylhydrazine assay. Redox Rep 14: 159–166, 2009.
22. Maarbjerg SJ, Sylow L, Richter E. Current understanding of increased insulin sensitivity after exercise-emerging candidates. Acta Physiol (Oxf) 202: 323–335, 2011.
23. Mascher H, Andersson H, Nilsson PA, Ekblom B, Blomstrand E. Changes in signalling pathways regulating protein synthesis in human muscle in the recovery period after endurance exercise. Acta Physiol (Oxf) 191: 67–75, 2007.
24. McConell GK, Kaur G, Falcão-Tebas F, Hong YH, Gatford KL. Acute exercise increases insulin sensitivity in adult sheep: a new pre-clinical model. Am J Physiol Regul Integr Comp Physiol 308: R500–R506, 2015.
25. Medved I, Brown MJ, Bjorksten AR, Leppik JA, Sostaric S, McKenna MJ. N-acetylcysteine infusion alters blood redox status but not time to fatigue during intense exercise in humans. J Appl Physiol 94: 1572–1582, 2003.
26. Medved I, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X, McKenna MJ. N-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individuals. J Appl Physiol 97: 1477–1485, 2004.
27. Merry T, Dywer R, Bradley E, Rattigan S, McConell G. Local hindlimb antioxidant infusion does not affect muscle glucose uptake during in situ contractions in rat. J Appl Physiol 108: 1275–1283, 2010.
28. Merry T, Wadley G, Stathis C, Garnham A, Rattigan S, Hargreaves M, McConell G. N-Acetylcysteine infusion does not affect glucose disposal during prolonged moderate-intensity exercise in humans. J Physiol 588: 1623–1634, 2010.
29. Merry TL, Steinberg GR, Lynch GS, McConell GK. Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK. Am J Physiol Endocrinol Metab 298: E577–E585, 2010.
30. Michailidis Y, Karagounis LG, Terzis G, Jamurtas AZ, Spengos K, Tsoukas D, Chatzinikolaou A, Mandalidis D, Stefanetti RJ, Papassotiriou I. Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise. Am J Clin Nutr 98: 233–245, 2013.
31. Mikines KJ, Sonne B, Peter A, Farrell BT, Galbo H. Effect of physical exercise on sensitivity and responsiveness to insulin in humans. Am J Physiol Endocrinol Metab 254: E248–E259, 1988.
32. Nagata M, Arimitsu N, Ito T, Sekimizu K. Antioxidant N-acetyl-Lcysteine inhibits erythropoietin-induced differentiation of erythroid progenitors derived from mouse fetal liver. Cell Biol Int 31: 252–256, 2007.
33. Petersen AC, McKenna MJ, Medved I, Murphy KT, Brown MJ, Della Gatta P, Cameron-Smith D. Infusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscle. Acta Physiol (Oxf) 204: 382–392, 2012.
34. Powers SK, Duarte J, Kavazis AN, Talbert EE. Reactive oxygen species are signalling molecules for skeletal muscle adaptation. Exp Physiol 95: 1–9, 2010.
35. Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G. Phosphorylation and activation of p70s6k by PDK 1. Science 279: 707–710, 1998.
36. Reyna SM, Tantiwong P, Cersosimo E, DeFronzo RA, Sriwijitkamol A, Musi N. Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulinresistant subjects. J Diabetes Res. 2013, PMID 107805, 8 pages; doi: 10.1155/2013/107805.
37. Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn C, Blüher M. Antioxidants prevent healthpromoting effects of physical exercise in humans. Proc Natl Acad Sci USA 106: 8665–8670, 2009.
38. Romero-Calvo I, Ocón B, Martínez-Moya P, Suárez MD, Zarzuelo A, Martínez-Augustin O, de Medina FS. Reversible Ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem 401: 318–320, 2010.
39. Sandström M, Zhang S, Bruton J, Silva J, Reid M, Westerblad H, Katz A. Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle. J Physiol 575: 251–262, 2006.
40. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098–1101, 2005.
41. Sarbassov DD, Sabatini DM. Redox regulation of the nutrient-sensitive raptor-mTOR pathway and complex. J Biol Chem 280: 39505–39509, 2005.
42. Scheele C, Nielsen S, Pedersen BK. ROS and myokines promote muscle adaptation to exercise. Trends Endocrinol Metab 20: 95–99, 2009.
43. Schweitzer GG, Arias EB, Cartee GD. Sustained postexercise increases in AS160 Thr642 and Ser588 phosphorylation in skeletal muscle without sustained increases in kinase phosphorylation. J Appl Physiol 113: 1852–1861, 2012.
44. Sen CK, Marin E, Kretzschmar M, Hanninen O. Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization. J Appl Physiol 73: 1265–1272, 1992.
45. Stepto NK, Benziane B, Wadley GD, Chibalin AV, Canny BJ, Eynon N, McConell GK. Short-term intensified cycle training alters acute and chronic responses of PGC1 and Cytochrome C oxidase IV to exercise in human skeletal muscle. PLoS One 7: e53080, 2012.
46. Strobel NA, Peake JM, Matsumoto A, Marsh SA, Coombes JS, Wadley GD. Antioxidant supplementation reduces skeletal muscle mitochondrial biogenesis. Med Sci Sports Exerc 43: 1017–1024, 2011.
47. Tiganis T. Reactive oxygen species and insulin resistance: the good, the bad and the ugly. Trends Pharmacol Sci 32: 82–89, 2011.
48. Treebak JT, Frøsig C, Pehmøller C, Chen S, Maarbjerg SJ, Brandt N, MacKintosh C, Zierath J, Hardie D, Kiens B. Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle. Diabetologia 52: 891–900, 2009.
49. Trenerry MK, Carey KA, Ward AC, Cameron-Smith D. STAT3 signaling is activated in human skeletal muscle following acute resistance exercise. J Appl Physiol 102: 1483–1489, 2007.
50. Trewin AJ, Petersen AC, Billaut F, McQuade LR, McInerney BV, Stepto NK. N-acetylcysteine alters substrate metabolism during highintensity cycle exercise in well-trained humans. Appl Physiol Nutr Metab 1–11, 2013.
51. Wadley GD, McConell GK. High-dose antioxidant vitamin C supplementation does not prevent acute exercise-induced increases in markers of skeletal muscle mitochondrial biogenesis in rats. J Appl Physiol 108: 1719, 2010.
52. Watt MJ, Howlett KF, Febbraio MA, Spriet LL, Hargreaves M. Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans. J Physiol 534: 269–278, 2001.
53. Wilkinson SB, Phillips SM, Atherton PJ, Patel R, Yarasheski KE, Tarnopolsky MA, Rennie MJ. Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol 586: 3701–3717, 2008.
54. Wojtaszewski JF, Hansen BF, Kiens B, Markuns J, Goodyear L, Richter E. Insulin signaling and insulin sensitivity after exercise in human skeletal muscle. Diabetes 49: 325–331, 2000.
55. Wojtaszewski JF, Hansen BF, Kiens B, Richter EA. Insulin signaling in human skeletal muscle: time course and effect of exercise. Diabetes 46: 1775–1781, 1997.
56. Yfanti C, Akerström T, Nielsen S, Nielsen AR, Mounier R, Mortensen OH, Lykkesfeldt J, Rose AJ, Fischer CP, Pedersen BK. Antioxidant supplementation does not alter endurance training adaptation. Med Sci Sports Exerc 42: 1388–1395, 2010.
57. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94: 909–950