Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle
| Autor: | David E. James, Benjamin L. Parker, Jesper B. Birk, Lea Bruhn, Marie F. Rosschou, Nils J. Færgeman, Kei Sakamoto, Joachim Fentz, Mads B. Hansen, Erik A. Richter, Bente Kiens, Marc Foretz, Jørgen F. P. Wojtaszewski, Janne R. Hingst, Jesper F. Havelund, Benoit Viollet, Jørgen Arendt Jensen |
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| Přispěvatelé: | University of Copenhagen = Københavns Universitet (KU), Protocols and applications for the Internet (PLANETE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Dundee, University of Southern Denmark (SDU), The University of Sydney, Section of Molecular Physiology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Proteomics MESH: Signal Transduction MESH: Dietary Carbohydrates Glucose uptake medicine.medical_treatment MESH: Carbohydrate Metabolism MESH: Glycogen MESH: Physical Conditioning Animal chemistry.chemical_compound Mice Insulin MESH: Animals Phosphorylation MESH: Muscle Skeletal Glycogen biology MESH: Proteomics [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] MESH: Glucose medicine.anatomical_structure Glycogen Synthase Carbohydrate Metabolism Signal Transduction MESH: Carbohydrates Adult Glycogen synthase (GS) medicine.medical_specialty lcsh:Internal medicine MESH: Mice Transgenic Carbohydrates Mice Transgenic MESH: Insulin Carbohydrate metabolism 03 medical and health sciences Internal medicine Physical Conditioning Animal AMP-activated protein kinase (AMPK) medicine Dietary Carbohydrates Animals Humans [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Glycogen synthase lcsh:RC31-1245 Muscle Skeletal TBC1 domain family member 4 (TBC1D4) Molecular Biology Exercise MESH: Mice Insulin action MESH: Glycogen Synthase MESH: Humans MESH: Phosphorylation AMPK Skeletal muscle MESH: Adult [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Cell Biology MESH: Male 030104 developmental biology Endocrinology Glucose chemistry MESH: Exercise biology.protein Supercompensation |
| Zdroj: | Molecular metabolism Molecular metabolism, Elsevier, 2018, 16, pp.24-34. ⟨10.1016/j.molmet.2018.07.001⟩ Molecular Metabolism, Vol 16, Iss, Pp 24-34 (2018) Hingst, J R, Bruhn, L, Hansen, M B, Rosschou, M F, Birk, J B, Fentz, J, Foretz, M, Viollet, B, Sakamoto, K, Færgeman, N J, Havelund, J F, Parker, B L, James, D E, Kiens, B, Richter, E A, Jensen, J & Wojtaszewski, J F P 2018, ' Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle ', Molecular Metabolism, vol. 16, pp. 24-34 . https://doi.org/10.1016/j.molmet.2018.07.001 Hingst, J R, Bruhn, L, Hansen, M B, Rosschou, M F, Birk, J B, Fentz, J, Foretz, M, Viollet, B, Sakamoto, K, Færgeman, N J, Havelund, J F, Parker, B L, James, D E, Kiens, B, Richter, E A, Jensen, J & Wojtaszewski, J 2018, ' Exercise-induced molecular mechanisms promoting glycogen supercompensation in human skeletal muscle ', Molecular Metabolism, vol. 16, pp. 24-34 . https://doi.org/10.1016/j.molmet.2018.07.001 |
| ISSN: | 2212-8778 |
| DOI: | 10.1016/j.molmet.2018.07.001⟩ |
| Popis: | Objective: A single bout of exercise followed by intake of carbohydrates leads to glycogen supercompensation in prior exercised muscle. Our objective was to illuminate molecular mechanisms underlying this phenomenon in skeletal muscle of man. Methods: We studied the temporal regulation of glycogen supercompensation in human skeletal muscle during a 5 day recovery period following a single bout of exercise. Nine healthy men depleted (day 1), normalized (day 2) and supercompensated (day 5) muscle glycogen in one leg while the contralateral leg served as a resting control. Euglycemic hyperinsulinemic clamps in combination with leg balance technique allowed for investigating insulin-stimulated leg glucose uptake under these 3 experimental conditions. Cellular signaling in muscle biopsies was investigated by global proteomic analyses and immunoblotting. We strengthened the validity of proposed molecular effectors by follow-up studies in muscle of transgenic mice. Results: Sustained activation of glycogen synthase (GS) and AMPK in combination with elevated expression of proteins determining glucose uptake capacity were evident in the prior exercised muscle. We hypothesize that these alterations offset the otherwise tight feedback inhibition of glycogen synthesis and glucose uptake by glycogen. In line with key roles of AMPK and GS seen in the human experiments we observed abrogated ability for glycogen supercompensation in muscle with inducible AMPK deletion and in muscle carrying a G6P-insensitive form of GS in muscle. Conclusion: Our study demonstrates that both AMPK and GS are key regulators of glycogen supercompensation following a single bout of glycogen-depleting exercise in skeletal muscle of both man and mouse. Keywords: AMP-activated protein kinase (AMPK), TBC1 domain family member 4 (TBC1D4), Glycogen synthase (GS), Glucose uptake, Exercise, Insulin action |
| Databáze: | OpenAIRE |
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