Influence of muscle glycogen on glycogenolysis and glucose uptake during exercise in humans
Abstract
To examine the effects of alterations in preexercise muscle glycogen availability on glycogenolysis and glucose uptake during exercise, 12 active but untrained men [22.8 +/- 1.6 (SE) yr, 71.7 +/- 2.0 kg, peak pulmonary oxygen uptake 3.85 +/- 0.16 l/min] were studied during 40 min of cycle ergometer exercise at 65–70% peak pulmonary oxygen uptake on two separate occasions, at least 1 wk apart. Preexercise muscle glycogen concentrations were manipulated by having the subjects perform glycogen-lowering exercise either 24 or 48 h before a trial, in combination with either high or low dietary carbohydrate intake. In series 1 (n = 7), increasing muscle glycogen from 90.3 +/- 6.0 to 124.7 +/- 10.8 mmol/kg wet wt increased muscle glycogenolysis during exercise (62.7 +/- 7.9 vs. 49.1 +/- 6.6 mmol/kg; P < 0.05). Similarly, in series 2 (n = 5) when muscle glycogen was reduced from 96.2 +/- 6.6 to 53.7 +/- 6.0 mmol/kg, glycogen utilization during exercise was reduced from 51.8 +/- 4.6 to 28.3 +/- 3.8 mmol/kg (P < 0.05). The altered muscle glycogen utilization was associated with alterations in carbohydrate oxidation during exercise, without effect on tracer ([3H]glucose)-determined glucose uptake. These results indicate that preexercise muscle glycogen availability influences muscle glycogenolysis, but not glucose uptake, during exercise.
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Exercise performed with higher starting muscle glycogen concentrations elicits higher rates of net muscle glycogenolysis.
“Consequently, exercise performed with higher starting muscle glycogen concentrates elicits higher rates of net muscle glycogenolysis (79).”
From Carbohydrate ingestion during prolonged exercise and net skeletal muscle glycogen utilization: A meta-analysis. (2026) · cites this paper as [79]
Elevations in the rate of degradation of glycogen during exercise are exponentially related to pre-exercise muscle glycogen concentrations.
“with elevations in the rate of degradation of glycogen during exercise being exponentially related to pre-exercise muscle glycogen concentrations [69,70].”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [69]
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InfluentialSkeletal Muscle Metabolism During Exercise In Humans
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“, which is supported by previous studies (30,31).”
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Oral [13C]glucose oxidation during prolonged exercise after high- and low-carbohydrate diets
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BackgroundResultFell, J. M., Hearris, M. A., Ellis, D. G., Moran, J. E. P., Jevons, E. F. P., Owens, D. J., Strauss, J. A., Cocks, M. S., Louis, J. B., Shepherd, S. O., et al. (2021) · The Journal of Physiology · doi:10.1113/jp281127 · Cited by 37 · see citing works
“a true CHO loading protocol as well as consumption of a pre-exercise high CHO meal), it is possible that any potential regulatory effects of consuming CHO ‘during’ exercise are offset by the effects of higher pre-exercise muscle glycogen availability on absolute muscle glycogen utilisation (Hargreaves et al. 1995; Ark…”
BackgroundProlonged cycling reduces power output at the moderate-to-heavy intensity transition
Stevenson, J. D., Kilding, A. E., Plews, D. J., & Maunder, E. (2022) · European Journal of Applied Physiology · doi:10.1007/s00421-022-05036-9 · Cited by 41 · see citing works
“Larger increases in fat oxidation following prolonged exercise may reflect greater muscle glycogen depletion (Hargreaves et al. 1995), and glycogen depletion may as discussed negatively impact contractile function and in turn efficiency at the level of the muscle fibre (Ørtenblad et al.”
BackgroundMuscle Ionic Shifts During Exercise: Implications for Fatigue and Exercise Performance
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“This demonstrates for the first time that glycogen concentration may be a factor in the regulation in postmortem muscle glycolysis and supports findings within the exercise physiology literature (Hargreaves et al., 1995; Hespel & Richter, 1990, 1992; Richter & Galbo, 1986; Vandenberghe et al., 1999; Shearer et al., 20…”
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Watt, M. J., & Hargreaves, M. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00098.2002 · Cited by 35 · see citing works
“Under such conditions, exercise results in less muscle glycogenolysis (9) and G-6-P accumulation (29).”
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“(13) report preexercise values of 96 μmol/g wet wt after exercise and 24 h on a high-CHO diet and 54 μmol/g wet wt after exercise and 24 h on a low-CHO diet.”
BackgroundExercise, muscle, and <scp>CHO</scp> metabolism
Hargreaves, M. (2015) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12607 · Cited by 33 · see citing works
“Muscle glycogen use during exercise is also directly related to the pre-exercise muscle glycogen level (Hargreaves et al., 1995) and there is evidence that glycogen phosphorylase activity is increased by higher muscle glycogen levels.”
BackgroundSelf-citationTaylor, C. W., Higham, D., Close, G. L., & Morton, J. P. (2011) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.21.5.410 · Cited by 31 · see citing works
Manetta, J., Brun, J.-F., Prefaut, C., & Mercier, J. (2005) · Metabolism · doi:10.1016/j.metabol.2004.12.002 · Cited by 30 · see citing works
“Diminished baseline muscle glycogen stores have been noted in elderly subjects [28], and this decline may have influenced the use of muscle glycogen in our middleaged subjects because the rate of glycogenolysis during exercise is closely related to initial content [29].”
BackgroundMargolis, L. M., Karl, J. P., Wilson, M. A., Coleman, J. L., Whitney, C. C., & Pasiakos, S. M. (2021) · Metabolites · doi:10.3390/metabo11120828 · Cited by 30 · see citing works
Diurnal Regulation of Peripheral Glucose Metabolism: Potential Effects of Exercise Timing
Mancilla, R., Krook, A., Schrauwen, P., & Hesselink, M. K. C. (2020) · Obesity · doi:10.1002/oby.22811 · Cited by 29 · see citing works
“On the other hand, it is important to highlight that exercise-induced skeletal muscle glycogen turnover is governed by absolute glycogen content (66,67), which is expected to be higher in the evening.”
BackgroundClaassen, A., Lambert, E. V., Bosch, A. N., Rodger, I. M., Gibson, A. S. C., & Noakes, T. D. (2005) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.15.2.97 · Cited by 29 · see citing works
Kent, J. A., Ørtenblad, N., Hogan, M. C., Poole, D. C., & Musch, T. I. (2016) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001052 · Cited by 30 · see citing works
“performance, but also increase muscle glycogen content (39).”
BackgroundHyperthermia, but not muscle water deficit, increases glycogen use during intense exercise
Fernández-Elías, V. E., Hamouti, N., ORTEGA, J. F., & Mora‐Rodríguez, R. (2015) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.12368 · Cited by 26 · see citing works
Zanker, C. L., Swaine, I., Castell, L. M., et al. (1997) · European Journal of Applied Physiology · doi:10.1007/s004210050202 · Cited by 25 · see citing works
“Nevertheless, a similar regime has been shown to e ect a signi®cant reduction in muscle glycogen in other studies which have quanti®ed muscle glycogen using the biopsy technique (Gollnick et al. 1974; Hargreaves et al. 1995).”
MethodMaunder, E., Plews, D. J., Wallis, G. A., Brick, M. J., Leigh, W. B., Chang, W., Stewart, T. I., Watkins, C. M., & Kilding, A. E. (2021) · European Journal of Applied Physiology · doi:10.1007/s00421-021-04820-3 · Cited by 25 · see citing works
“1967), and glycogen phosphorylase activation (Hespel and Richter 1992), and consequently glycogenolysis (Hargreaves et al. 1995), is related to glycogen availability.”
BackgroundProeyen, K. V., Szlufcik, K., Nielens, H., Deldicque, L., Dyck, R. V., Ramaekers, M., & Hespel, P. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01459.2010 · Cited by 24 · see citing works
Gallo, G., Faelli, E. L., Ruggeri, P., Filipas, L., Codella, R., Plews, D. J., & Maunder, E. (2024) · European Journal of Applied Physiology · doi:10.1007/s00421-024-05440-3 · Cited by 26 · see citing works
“…exhibiting large increases in fatty acid oxidation during prolonged exercise, which likely reflects greater glycogen depletion due to the autoregulatory nature of carbohydrate metabolism (Hargreaves et al. 1995), saw the largest reductions in gross cycling efficiency (Stevenson et al. 2022).”
BackgroundKowalchuk, J. M., Smith, S. A., Weening, B. S., et al. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.1.200 · Cited by 23 · see citing works
“In addition, muscle glycogen levels were reduced by ;50% before exercise began, which also may have contributed to a lower rate of glycolysis because the glycolytic rate may be influenced by the initial muscle glycogen content (9).”
BackgroundMikulski, T., Ziemba, A. W., & Nazar, K. (2008) · PubMed · Cited by 22 · see citing works
Zderic, T. W., Schenk, S., Davidson, C. J., Byerley, L. O., & Coyle, E. F. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00302.2004 · Cited by 20 · see citing works
Repeated muscle glycogen supercompensation with four days’ recovery between exhaustive exercise
Doering, T. M., Cox, G. R., Areta, J. L., & Coffey, V. G. (2019) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2019.03.009 · Cited by 19 · see citing works
Transforming growth factor-β in the brain regulates fat metabolism during endurance exercise
Ishikawa, T., Mizunoya, W., Shibakusa, T., Inoue, K., & Fushiki, T. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00039.2006 · Cited by 19 · see citing works
“However, glycogenolysis and CHO oxidation during exercise are enhanced by the prior augmentation of the glycogen content in muscle (14, 35, 38).”
BackgroundHamzah, S. H., Higgins, S., Abraham, T. A., Taylor, P., Vizbaraitė, D., & Malkova, D. (2009) · Journal of Sports Sciences · doi:10.1080/02640410903134115 · Cited by 17 · see citing works
Helge, J. W., Watt, P., Richter, E. A., Rennie, M. J., & Kiens, B. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00420.2002 · Cited by 17 · see citing works
“Still, because higher preexercise muscle glycogen stores in the group switching from fat to carbohydrate diet by itself would be expected to increase muscle glycogen breakdown (15), it could be argued that identical muscle glycogen breakdown rates in the two groups in fact represent a relative impairment of breakdown…”
BackgroundOliver, J. M., Almada, A. L., Van Eck, L. E., Shah, M., Mitchell, J. B., Jones, M. T., Jagim, A. R., & Rowlands, D. S. (2016) · PLOS ONE · doi:10.1371/journal.pone.0163009 · Cited by 16 · see citing works
“Though not measured, the carbohydrate restricted diet used in that study [8] had been reported previously to reduce muscle glycogen concentration [10].”
Polyviou, T. P., Pitsiladis, Y. P., Lee, W. C., Takas, P., Hambly, C., Speakman, J. R., & Malkova, D. (2012) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-9-29 · Cited by 16 · see citing works
“It is well established that increased dietary carbohydrate intake for several days increases muscle glycogen concentration [35,36] and that energy substrate selection during exercise to a great degree depends on muscle glycogen availability [37,38].”
BackgroundChristmass, M. A., Dawson, B., Goodman, C., & Arthur, P. G. (2001) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2001.00814.x · Cited by 15 · see citing works
Regulation of glycogen breakdown by glycogen level in contracting rat muscle
Vandenberghe, Richter, E. A., & Hespel, P. (1999) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1999.00506.x · Cited by 15 · see citing works
Carbohydrates and Exercise Performance
Hargreaves, M. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1996.tb03909.x · Cited by 13 · see citing works
Self-citationFerreira, G. A., Felippe, L. C., Silva, R. L. S., Bertuzzi, R., De-Oliveira, F. R., Pires, F. O., & Lima‐Silva, A. E. (2018) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20186964 · Cited by 13 · see citing works
“This combination of glycogen-depletion exercise and diet manipulation was applied to produce greater differences in endogenous CHO availability before the HIE (12).”
Diet and Training in the Week Before Competition
Kiens, B. (2001) · Canadian Journal of Applied Physiology · doi:10.1139/h2001-042 · Cited by 13 · see citing works
Effect of dietary carbohydrate content on blood glucose levels of swimmers during training.
Soultanakis, H. N., & Platanou, T. I. (2008) · PubMed · Cited by 12 · see citing works
Muscle Ionic Shifts During Exercise: Implications for Fatigue and Exercise Performance
Hostrup, M., Cairns, S. P., & Bangsbo, J. (2021) · Comprehensive physiology · doi:10.1002/j.2040-4603.2021.tb00169.x · Cited by 12 · see citing works
Muscle Glycogen Utilization During an Australian Rules Football Game
Routledge, H. E., Leckey, J. J., Lee, M. J.-C., GARNHAM, A. P., Graham, S. R., Burgess, D. J., Burke, L. M., Erskine, R. M., Close, G. L., & Morton, J. P. (2018) · International Journal of Sports Physiology and Performance · doi:10.1123/ijspp.2018-0106 · Cited by 12 · see citing works
“…such inter-individual variation in glycogen use may be due to differences in total distance covered, duration, pre-match muscle glycogen concentrations 11 , training status and muscle oxidative capacity 12 , it is noteworthy that Player B also consumed an additional 88 g of CHO during match play.”
Rannou, F., Leschiera, R., Giroux-Metges, M. A., & Pennec, J. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00944.2011 · Cited by 12 · see citing works
- Authors
- Hargreaves, M., McConell, G., & Proietto, J.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 1995-01-01
- Volume
- 78
- Issue
- 1
- Pages
- 288-292
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2174039389
- Cited by
- 172
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 11 · 2020: 7 · 2019: 5 · 2018: 10 · 2017: 2 · 2016: 5 · 2015: 6 · 2014: 3 · 2013: 6 · 2012: 5
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- muscle glycogen, glycogenolysis, glucose uptake, physical activity, glycogen depletion, carbohydrate intake, carbohydrate oxidation, untrained men, cycle ergometry
- MeSH terms
- Adult, Carbon Dioxide, Dietary Carbohydrates, Fatty Acids, Nonesterified, Glucose, Glycogen, Humans, Insulin, Kinetics, Lactates, Male, Oxygen Consumption, Exercise, Muscle, Skeletal, Lactic Acid
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