Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-13T07:44:10.207Z Has data issue: false hasContentIssue false
  • English
  • Français

Regulation of glycogen synthase activity and phosphorylation by exercise

Published online by Cambridge University Press:  05 March 2007

Jakob N. Nielsen  and
Jørgen F. P. Wojtaszewski
Jakob N. Nielsen
Affiliation:
Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
Jørgen F. P. Wojtaszewski*
Affiliation:
Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
*
*Corresponding author: Dr J. F. P. Wojtaszewski Fax: +45 35 32 16 00, Email: jwojtaszewski@aki.ku.dk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Glycogen synthase (GS) catalyses the rate-limiting step of UDP-glucose incorporation into glycogen. Exercise is a potent regulator of GS activity, leading to activation of GS immediately after exercise promoting glycogen repletion by mechanisms independent of insulin. The incorporation of UDP-glucose is energy demanding, and during intense exercise GS is deactivated, diminishing energy utilization but also increasing the potential for glycogen breakdown. An apparent activation of GS is observed during moderate exercise, which could be considered as a potential waste of energy, although the cellular capacity for glycogen breakdown is considerably higher than that for glycogen synthesis. The understanding of this complex regulation of GS activity in response to exercise is just at its beginning. In the present review potential mechanisms by which exercise regulates GS activity are described, factors that may promote GS activation and factors that may deactivate GS are discussed, pointing to the view that GS activity during exercise is the result of the relative strength of these opposing factors.

Keywords

ExerciseContractionSkeletal muscleGlycogen synthasePhosphorylation
Type
Symposium 1: Exercise signalling pathways controlling fuel oxidation during and after exercise
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 233 - 237
Copyright
Copyright © The Nutrition Society 2004

References

Aschenbach, WG, Suzuki, Y, Breeden, K, Prats, C, Hirshman, MF, Dufresne, SD, Sakamoto, K, Vilardo, PG, Steele, M, Kim, JH, Jing, SS, Goodyear, LJ & DePaoli-Roach, AA (2001) The muscle-specific protein phosphatase PP1G/R GL(GM) is essential for activation of glycogen synthase by exercise. Journal of Biological Chemistry 276, 39959–39967.CrossRefGoogle Scholar
Bloch, G, Chase, JR, Meyer, DB, Avison, MJ, Shulman, GI & Shulman, RG (1994) In vivo regulation of rat muscle glycogen resynthesis after intense exercise. American Journal of Physiology 266, E85–E91.Google ScholarPubMed
Brady, MJ & Saltiel, AR (2001) The role of protein phosphatase-1 in insulin action. Recent Progress in Hormone Research 56, 157–173.CrossRefGoogle ScholarPubMed
Carling, D & Hardie, DG (1989) The substrate and sequence specificity of the AMP-activated protein kinase. Phosphorylation of glycogen synthase and phosphorylase kinase. Biochimica et Biophysica Acta 1012, 81–86.CrossRefGoogle ScholarPubMed
Chasiotis, D, Brandt, R, Harris, RC & Hultman, E (1983a) Effects of beta-blockade on glycogen metabolism in human subjects during exercise. American Journal of Physiology 245, E166–E170.Google ScholarPubMed
Chasiotis, D, Sahlin, K & Hultman, E (1982) Regulation of glycogenolysis in human muscle at rest and during exercise. Journal of Applied Physiology 53, 708–715.CrossRefGoogle ScholarPubMed
Chasiotis, D, Sahlin, K & Hultman, E (1983b) Regulation of glycogenolysis in human muscle in response to epinephrine infusion. Journal of Applied Physiology 54, 45–50.CrossRefGoogle ScholarPubMed
Chen, Z, Heierhorst, J, Mann, RJ, Mitchelhill, KI, Michell, BJ, Witters, LA, Lynch, GS, Kemp, BE & Stapleton, D (1999) Expression of the AMP-activated protein kinase beta1 and beta2 subunits in skeletal muscle. FEBS Letters 460, 343–348.CrossRefGoogle ScholarPubMed
Cohen, P (1978) The role of cyclic-AMP-dependent protein kinase in the regulation of glycogen metabolism in mammalian skeletal muscle. Current Topics in Cellular Regulation 14, 117–196.CrossRefGoogle ScholarPubMed
Danforth, WH (1965) Glycogen synthase activity in skeletal muscle. Interconversion of two forms and control of glycogen synthesis. Journal of Biological Chemistry 240, 588–593.CrossRefGoogle ScholarPubMed
Hiraga, A & Cohen, P (1986) Phosphorylation of the glycogen-binding subunit of protein phosphatase-1G by cyclic-AMP-dependent protein kinase promotes translocation of the phosphatase from glycogen to cytosol in rabbit skeletal muscle. European Journal of Biochemistry 161, 763–769.CrossRefGoogle ScholarPubMed
Hojlund, K, Staehr, P, Hansen, BF, Green, KA, Hardie, DG, Richter, EA, Beck-Nielsen, H & Wojtaszewski, JFP (2003) Increased phosphorylation of skeletal muscle glycogen synthase at NH2-terminal sites during physiological hyperinsulinemia in type 2 diabetes. Diabetes 52, 1393.CrossRefGoogle ScholarPubMed
Jiao, Y, Shashkin, P & Katz, A (2001) A new glycogen synthase activity ratio in skeletal muscle: effects of exercise and insulin. Life Sciences 69, 891–900.CrossRefGoogle ScholarPubMed
Marchand-Brustel, Y, Gautier, N, Cormont, M & Van Obberghen, E (1995) Wortmannin inhibits the action of insulin but not that of okadaic acid in skeletal muscle: comparison with fat cells. Endocrinology 136, 3564–3570.CrossRefGoogle Scholar
Markuns, JF, Wojtaszewski, JF & Goodyear, LJ (1999) Insulin and exercise decrease glycogen synthase kinase-3 activity by different mechanisms in rat skeletal muscle. Journal of Biological Chemistry 274, 24896–24900.CrossRefGoogle ScholarPubMed
Montell, E, Arias, A, Gomez-Foix, AM (1999) Glycogen depletion rather than glucose 6-P increments controls early glycogen recovery in human cultured muscle. American Journal of Physiology 276, R1489–R1495.Google ScholarPubMed
Nielsen, JN, Derave, W, Kristiansen, S, Ralston, E, Ploug, T & Richter, EA (2001) Glycogen synthase localization and activity in rat skeletal muscle is strongly dependent on glycogen content. Journal of Physiology (London) 531, 757–769.CrossRefGoogle ScholarPubMed
Parker, GJ, Lund, KC, Taylor, RP & McClain, DA (2003) Insulin resistance of glycogen synthase mediated by O-linked N-acetylglucosamine. Journal of Biological Chemistry 278, 10022–10027.CrossRefGoogle ScholarPubMed
Parker, PJ, Caudwell, FB & Cohen, P (1983) Glycogen synthase from rabbit skeletal muscle; effect of insulin on the state of phosphorylation of the seven phosphoserine residues in vivo. European Journal of Biochemistry 130, 227–234.CrossRefGoogle ScholarPubMed
Roach, PJ (2002) Glycogen and its metabolism. Current Molecular Medicine 2, 101–120.CrossRefGoogle ScholarPubMed
Roach, PJ & Larner, J (1976) Rabbit skeletal muscle glycogen synthase. II. Enzyme phosphorylation state and effector concentrations as interacting control parameters. Journal of Biological Chemistry 251, 1920–1925.CrossRefGoogle ScholarPubMed
Roach, PJ, Takeda, Y & Larner, J (1976) Rabbit skeletal muscle glycogen synthase. I. Relationship between phosphorylation state and kinetic properties. Journal of Biological Chemistry 251, 1913–1919.CrossRefGoogle ScholarPubMed
Sakamoto, K, Aschenbach, WG, Hirshman, MF & Goodyear, LJ (2003) Akt signaling in skeletal muscle: Regulation by exercise and passive stretch. American Journal of Physiology 285, E1081–E1088.Google ScholarPubMed
Sakamoto, K, Hirshman, MF, Aschenbach, WG & Goodyear, LJ (2002) Contraction regulation of Akt in rat skeletal muscle. Journal of Biological Chemistry 277, 11910–11917.CrossRefGoogle ScholarPubMed
Skurat, AV & Dietrich, AD (2003) DYRK Family protein kinases phosphorylates Ser-640 in muscle glycogen synthase. Diabetes 52, 1852.Google Scholar
Wojtaszewski, JFP, Higaki, Y, Hirshman, MF, Michael, MD, Dufresne, SD, Kahn, CR & Goodyear, LJ (1999a) Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice. Journal of Clinical Investigation 104, 1257–1264.CrossRefGoogle ScholarPubMed
Wojtaszewski, JFP, Jorgensen, SB, Hellsten, Y, Hardie, DG & Richter, EA (2002) Glycogen-dependent effects of 5-aminoimidazole-4-carboxamide (AICA)-riboside on AMP-activated protein kinase and glycogen synthase activities in rat skeletal muscle. Diabetes 51, 284–292.CrossRefGoogle ScholarPubMed
Wojtaszewski, JFP, Lynge, J, Jakobsen, AB, Goodyear, LJ & Richter, EA (1999b) Differential regulation of MAP kinase by contraction and insulin in skeletal muscle: metabolic implications. American Journal of Physiology 277, E724–E732.Google ScholarPubMed
Wojtaszewski, JFP, Nielsen, P, Kiens, B & Richter, EA (2001) Regulation of glycogen synthase kinase-3 in human skeletal muscle: effects of food intake and bicycle exercise. Diabetes 50, 265–269.CrossRefGoogle ScholarPubMed