The Effect of Carbohydrate Ingestion Following Eccentric Resistance Exercise on AKT/mTOR and ERK Pathways: A Randomized, Double-Blinded, Crossover Study

in International Journal of Sport Nutrition and Exercise Metabolism
Vandre C. Figueiredo * , 1 , Michelle M. Farnfield * , 2 , Megan L.R. Ross * , 3 , 4 , Petra Gran * , 2 , Shona L. Halson * , 4 , Jonathan M. Peake * , 5 , 6 , David Cameron-Smith * , 1 , 7 , and James F. Markworth * , 1 , 8
View More View Less
  • 1 University of Auckland
  • 2 Deakin University
  • 3 Australian Catholic University
  • 4 Australian Institute of Sport
  • 5 Queensland Academy of Sport
  • 6 Queensland University of Technology
  • 7 AgResearch
  • 8 University of Michigan
DOI:
https://doi.org/10.1123/ijsnem.2019-0075
Keywords:
clinical trial; insulin; muscle hypertrophy; protein synthesis; recovery; skeletal muscle
In Print:
Volume 29: Issue 6
Pages:
664–670
Restricted access

Purchase article

USD  $24.95

Student 1 year online subscription

USD  $88.00

1 year online subscription

USD  $118.00

Student 2 year online subscription

USD  $168.00

2 year online subscription

USD  $224.00
Subscribe to this Journal

  • Purchase article

    USD  $24.95

  • Student 1 year online subscription

    USD  $88.00

  • 1 year online subscription

    USD  $118.00

  • Student 2 year online subscription

    USD  $168.00

  • 2 year online subscription

    USD  $224.00

Purpose: To determine the acute effects of carbohydrate (CHO) ingestion following a bout of maximal eccentric resistance exercise on key anabolic kinases of mammalian target of rapamycin and extracellular signal-regulated kinase (ERK) pathways. The authors’ hypothesis was that the activation of anabolic signaling pathways known to be upregulated by resistance exercise would be further stimulated by the physiological hyperinsulinemia resulting from CHO supplementation. Methods: Ten resistance-trained men were randomized in a crossover, double-blind, placebo (PLA)-controlled manner to ingest either a noncaloric PLA or 3 g/kg of CHO beverage throughout recovery from resistance exercise. Muscle biopsies were collected at rest, immediately after a single bout of intense lower body resistance exercise, and after 3 hr of recovery. Results: CHO ingestion elevated plasma glucose and insulin concentrations throughout recovery compared with PLA ingestion. The ERK pathway (phosphorylation of ERK1/2 [Thr202/Tyr204], RSK [Ser380], and p70S6K [Thr421/Ser424]) was markedly activated immediately after resistance exercise, without any effect of CHO supplementation. The phosphorylation state of AKT (Thr308) was unchanged postexercise in the PLA trial and increased at 3 hr of recovery above resting with ingestion of CHO compared with PLA. Despite stimulating-marked phosphorylation of AKT, CHO ingestion did not enhance resistance exercise–induced phosphorylation of p70S6K (Thr389) and rpS6 (Ser235/236 and Ser240/244). Conclusion: CHO supplementation after resistance exercise and hyperinsulinemia does not influence the ERK pathway nor the mTORC1 target p70S6K and its downstream proteins, despite the increased AKT phosphorylation.

Figueiredo, Cameron-Smith, and Markworth are with Liggins Institute, University of Auckland, Auckland, New Zealand. Farnfield and Gran are with the School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia. Ross is with the Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia. Ross and Halson are with the Sport Science and Sports Medicine, Australian Institute of Sport, Belconnen, Australia. Peake is with Sports Performance Innovation and Knowledge Excellence, Queensland Academy of Sport, Brisbane, Australia, and School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. Cameron-Smith is with the Food & Bio-Based Products Group, AgResearch, Palmerston North, New Zealand. Markworth is also with the Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Markworth (jmarkwor@umich.edu) is corresponding author.

International Journal of Sport Nutrition and Exercise Metabolism

Cover International Journal of Sport Nutrition and Exercise Metabolism

  • Borsheim, E., Cree, M.G., Tipton, K.D., Elliott, T.A., Aarsland, A., & Wolfe, R.R. (2004). Effect of carbohydrate intake on net muscle protein synthesis during recovery from resistance exercise. Journal of Applied Physiology, 96(2), 674–678. PubMed ID: 14594866 doi:10.1152/japplphysiol.00333.2003

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Churchward-Venne, T.A., Burd, N.A., & Phillips, S.M. (2012). Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism. Nutrition & Metabolism, 9(1), 40. PubMed ID: 22594765 doi:10.1186/1743-7075-9-40

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Dreyer, H.C., Drummond, M.J., Pennings, B., Fujita, S., Glynn, E.L., Chinkes, D.L., . . . Rasmussen, B.B. (2008). Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. American Journal of Physiology. Endocrinology and Metabolism, 294(2), E392–E400. PubMed ID: 18056791 doi:10.1152/ajpendo.00582.2007

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Eliasson, J., Elfegoun, T., Nilsson, J., Köhnke, R., Ekblom, B., & Blomstrand, E. (2006). Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. American Journal of Physiology. Endocrinology and Metabolism, 291(6), E1197–E1205. PubMed ID: 16835402 doi:10.1152/ajpendo.00141.2006

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Evans, W.J., Phinney, S.D., & Young, V.R. (1982). Suction applied to a muscle biopsy maximizes sample size. Medicine & Science in Sports & Exercise, 14(1), 101–102. PubMed ID: 7070249

    • Search Google Scholar
    • Export Citation

  • Figueiredo, V.C., & Cameron-Smith, D. (2013). Is carbohydrate needed to further stimulate muscle protein synthesis/hypertrophy following resistance exercise? Journal of the International Society of Sports Nutrition, 10 , 42. PubMed ID: 24066806 doi:10.1186/1550-2783-10-42

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Figueiredo, V.C., Markworth, J.F., & Cameron-Smith, D. (2017). Considerations on mTOR regulation at serine 2448: Implications for muscle metabolism studies. Cellular and Molecular Life Sciences, 74(14), 2537–2545. PubMed ID: 28220207 doi:10.1007/s00018-017-2481-5

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Figueiredo, V.C., Roberts, L.A., Markworth, J.F., Barnett, M.P.G., Coombes, J.S., Raastad, T., . . . Cameron-Smith, D. (2016). Impact of resistance exercise on ribosome biogenesis is acutely regulated by post-exercise recovery strategies. Physiological Reports, 4(2), e12670. PubMed ID: 26818586 doi:10.14814/phy2.12670

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Glynn, E.L., Fry, C.S., Timmerman, K.L., Drummond, M.J., Volpi, E., & Rasmussen, B.B. (2013). Addition of carbohydrate or alanine to an essential amino acid mixture does not enhance human skeletal muscle protein anabolism. The Journal of Nutrition, 143(3), 307–314. doi:10.3945/jn.112.168203

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Hamer, H.M., Wall, B.T., Kiskini, A., De Lange, A., Groen, B.B.L., Bakker, J.A., . . . Van Loon, L.J.C. (2013). Carbohydrate co-ingestion with protein does not further augment post-prandial muscle protein accretion in older men. Nutrition & Metabolism, 10(1), 15. PubMed ID: 23351781 doi:10.1186/1743-7075-10-15

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Han, J.M., Jeong, S.J., Park, M.C., Kim, G., Kwon, N.H., Kim, H.K., . . . Kim, S. (2012). Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell, 149(2), 410–424. PubMed ID: 22424946 doi:10.1016/j.cell.2012.02.044

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Hemmings, B.A., & Restuccia, D.F. (2012). PI3K-PKB/Akt pathway. Cold Spring Harbor Perspectives in Biology, 4(9), a011189. doi:10.1101/cshperspect.a011189

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Hoppeler, H., Baum, O., Lurman, G., & Mueller, M. (2011). Molecular mechanisms of muscle plasticity with exercise. Comprehensive Physiology, 1(3), 1383–1412. PubMed ID: 23733647 doi:10.1002/cphy.c100042

    • Search Google Scholar
    • Export Citation

  • Hornberger, T.A. (2011). Mechanotransduction and the regulation of mTORC1 signaling in skeletal muscle. International Journal of Biochemistry and Cell Biology, 43(9), 1267–1276. PubMed ID: 21621634 doi:10.1016/j.biocel.2011.05.007

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Hulmi, J.J., Lockwood, C.M., & Stout, J.R. (2010). Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein. Nutrition & Metabolism, 7 , 51. PubMed ID: 20565767 doi:10.1186/1743-7075-7-51

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Iijima, Y., Laser, M., Shiraishi, H., Willey, C.D., Sundaravadivel, B., Xu, L., . . . Kuppuswamy, D. (2002). c-Raf/MEK/ERK pathway controls protein kinase C-mediated p70S6K activation in adult cardiac muscle cells. Journal of Biological Chemistry, 277(25), 23065–23075. PubMed ID: 11940578 doi:10.1074/jbc.M200328200

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Inoki, K., Li, Y., Xu, T., & Guan, K.L. (2003). Rheb GTpase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes & Development, 17(15), 1829–1834. PubMed ID: 12869586 doi:10.1101/gad.1110003

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002). TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nature Cell Biology, 4(9), 648–657. PubMed ID: 12172553 doi:10.1038/ncb839

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Kerksick, C.M., Arent, S., Schoenfeld, B.J., Stout, J.R., Campbell, B., Wilborn, C.D., . . . Antonio, J. (2017). International society of sports nutrition position stand: Nutrient timing. Journal of the International Society of Sports Nutrition, 14 , 33. PubMed ID: 28919842 doi:10.1186/s12970-017-0189-4

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Koopman, R. (2004). Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. American Journal of Physiology. Endocrinology and Metabolism, 288(4), E645–E653. doi:10.1152/ajpendo.00413.2004

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Koopman, R., Saris, W.H.M., Wagenmakers, A.J.M., van Loon, L.J.C., & Wagenmakers, A.J.M. (2007). Nutritional interventions to promote post-exercise muscle protein synthesis. Sports Medicine, 37(10), 895–906. doi:10.2165/00007256-200737100-00005

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Laplante, M., & Sabatini, D.M. (2013). mTOR signaling in growth control and disease. Cell, 149(2), 274–293. doi:10.1016/j.cell.2012.03.017

  • Miller, S.L., Tipton, K.D., Chinkes, D.L., Wolf, S.E., & Wolfe, R.R. (2003). Independent and combined effects of amino acids and glucose after resistance exercise. Medicine & Science in Sports & Exercise, 35(3), 449–455. PubMed ID: 12618575 doi:10.1249/01.MSS.0000053910.63105.45

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Miyazaki, M., McCarthy, J.J., Fedele, M.J., & Esser, K.A. (2011). Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling. The Journal of Physiology, 589(7), 1831–1846. doi:10.1113/jphysiol.2011.205658

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Moberg, M., Apró, W., Ohlsson, I., Pontén, M., Villanueva, A., Ekblom, B., & Blomstrand, E. (2014). Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females. Applied Physiology, Nutrition, and Metabolism, 39(2), 183–194. PubMed ID: 24476474 doi:10.1139/apnm-2013-0244

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Moore, D.R., Robinson, M.J., Fry, J.L., Tang, J.E., Glover, E.I., Wilkinson, S.B., . . . Phillips, S.M. (2009). Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. The American Journal of Clinical Nutrition, 89(1), 161–168. PubMed ID: 19056590 doi:10.3945/ajcn.2008.26401

    • Crossref
    • Search Google Scholar
    • Export Citation

  • O’Neil, T.K., Duffy, L.R., Frey, J.W., & Hornberger, T.A. (2009). The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. The Journal of Physiology, 587(14), 3691–3701. doi:10.1113/jphysiol.2009.173609

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Rahbek, S.K., Farup, J., Møller, A.B., Vendelbo, M.H., Holm, L., Jessen, N., & Vissing, K. (2014). Effects of divergent resistance exercise contraction mode and dietary supplementation type on anabolic signalling, muscle protein synthesis and muscle hypertrophy. Amino Acids, 46(10), 2377–2392. PubMed ID: 25005782 doi:10.1007/s00726-014-1792-1

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Rasmussen, B.B., Tipton, K.D., Miller, S.L., Wolf, S.E., & Wolfe, R.R. (2000). An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise. Journal of Applied Physiology, 88(2), 386–392. PubMed ID: 10658002 doi:10.1152/jappl.2000.88.2.386

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Ross, M.L.R., Halson, S.L., Suzuki, K., Garnham, A., Hawley, J.A., Cameron-Smith, D., & Peake, J.M. (2010). Cytokine responses to carbohydrate ingestion during recovery from exercise-induced muscle injury. Journal of Interferon & Cytokine Research, 30(5), 329–337. PubMed ID: 20187772 doi:10.1089/jir.2009.0079

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Roy, B.D., Tarnopolsky, M.A., MacDougall, J.D., Fowles, J., & Yarasheski, K.E. (1997). Effect of glucose supplement timing on protein metabolism after resistance training. Journal of Applied Physiology, 82(6), 1882–1888. PubMed ID: 9173954 doi:10.1152/jappl.1997.82.6.1882

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Sarbassov, D.D., Guertin, D.A., Ali, S.M., & Sabatini, D.M. (2005). Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307(5712), 1098–1101. doi:10.1126/science.1106148

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Saxton, R.A., & Sabatini, D.M. (2017). mTOR signaling in growth, metabolism, and disease. Cell, 168(6), 960–976. PubMed ID: 28283069 doi:10.1016/j.cell.2017.02.004

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Tipton, K.D., Ferrando, A.A., Phillips, S.M., Doyle, D. Jr., & Wolfe, R.R. (1999). Postexercise net protein synthesis in human muscle from orally administered amino acids. The American Journal of Physiology, 276(4), E628–E6 34. doi:10.1152/ajpendo.1999.276.4.E628

    • Search Google Scholar
    • Export Citation

  • Vander Haar, E., Lee, S.I., Bandhakavi, S., Griffin, T.J., & Kim, D.-H. (2007). Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nature Cell Biology, 9(3), 316–323. doi:10.1038/ncb1547

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Vincent, E.E., Elder, D.J.E., Thomas, E.C., Phillips, L., Morgan, C., Pawade, J., . . . Tavaré, J.M. (2011). Akt phosphorylation on Thr308 but not on Ser473 correlates with Akt protein kinase activity in human non-small cell lung cancer. British Journal of Cancer, 104(11), 1755–1761. PubMed ID: 21505451 doi:10.1038/bjc.2011.132

    • Crossref
    • Search Google Scholar
    • Export Citation

  • Wolfe, R.R. (2006). Skeletal muscle protein metabolism and resistance exercise. The Journal of Nutrition, 136(2), 525S–528S. PubMed ID: 16424140 doi:10.1093/jn/136.2.525S

    • Crossref
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 2420 827 133
Full Text Views 83 32 1
PDF Downloads 64 23 3