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Effect of Exercise Intensity on Skeletal Muscle AMPK Signaling in Humans
Abstract
The effect of exercise intensity on skeletal muscle AMP-activated protein kinase (AMPK) signaling and substrate metabolism was examined in eight men cycling for 20 min at each of three sequential intensities: low (40 ± 2% Vo2 peak), medium (59 ± 1% Vo2 peak), and high (79 ± 1% Vo2 peak). Muscle free AMP/ATP ratio only increased at the two higher exercise intensities (P < 0.05). AMPK α1 (1.5-fold) and AMPK α2 (5-fold) activities increased from low to medium intensity, with AMPK α2 activity increasing further from medium to high intensity. The upstream AMPK kinase activity was substantial at rest and only increased 50% with exercise, indicating that, initially, signaling through AMPK did not require AMPK kinase posttranslational modification. Acetyl-CoA carboxylase (ACC)-β phosphorylation was sensitive to exercise, increasing threefold from rest to low intensity, whereas neuronal NO synthase (nNOS)μ phosphorylation was only observed at the higher exercise intensities. Glucose disappearance (tracer) did not increase from rest to low intensity, but increased sequentially from low to medium to high intensity. Calculated fat oxidation increased from rest to low intensity in parallel with ACCβ phosphorylation, then declined during high intensity. These results indicate that ACCβ phosphorylation is especially sensitive to exercise and tightly coupled to AMPK signaling and that AMPK activation does not depend on AMPK kinase activation during exercise.
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“the phosphorylation of AMPK is not the most sensitive measure of AMPK activity”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [54]
In the citing paper
“a direct measure of activity or the phosphorylation of its downstream target acetyl-CoA carboxylase show both the allosteric activation by AMP or ADP and the effect of phosphorylation [54]”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [54]
In the citing paper
“the muscle AMP/ATP ratio and AMPK activity increases with exercise intensity [54].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [54]
In the citing paper
“Consistent with this, AMPK is activated during exercise in both rodents and humans [51-60], in an intensity-dependent manner [57,59-61].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [58]
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“With the caveat that the phosphorylation of AMPK is not the most sensitive measure of AMPK activity (a direct measure of activity or the phosphorylation of its downstream target acetyl-CoA carboxylase show both the allosteric activation by AMP or ADP and the effect of phosphorylation [54]), this suggests that another…”
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Metadata
- Authors
- Chen, Z.-P., Stephens, T. J., Murthy, S., Canny, B. J., Hargreaves, M., Witters, L. A., Kemp, B. E., & McConell, G. K.
- Affiliations
- St. Vincent’s Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia
- Monash University (AU)
- The University of Melbourne (AU)
- Deakin University (AU)
- Dartmouth College (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-09-01
- Volume
- 52
- Issue
- 9
- Pages
- 2205-2212
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2142716760
- Cited by
- 369
- References
- 55
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 10 · 2023: 11 · 2022: 18 · 2021: 12 · 2020: 26 · 2019: 16 · 2018: 16 · 2017: 15 · 2016: 17 · 2015: 18 · 2014: 20 · 2013: 20 · 2012: 14
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health
- National Health and Medical Research Council
- National Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-35712, R01DK035712)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- exercise intensity, AMPK, skeletal muscle, neuronal nitric oxide synthase, glucose disappearance, fat oxidation, substrate metabolism
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Adult, Physical Exertion, Fatty Acids, Nonesterified, Glucose, Humans, Male, Nitric Oxide, Oxygen Consumption, Phosphorylation, Protein Kinases, Rest, Signal Transduction, Muscle, Skeletal, Nitric Oxide Synthase, Nitric Oxide Synthase Type I
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