Cited by 122Metabolism, Diabetes, and CancerMuscle Physiology and DisordersExercise and Physiological Responses

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Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK

Merry, Troy L., Steinberg, Gregory R., Lynch, Gordon S., McConell, Glenn K.·2010·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00239.2009

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Abstract

Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPKα2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-l-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N G -monomethyl-l-arginine (l-NMMA). Contraction increased AMPKα2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and l-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and l-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPKα Thr 172 phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or l-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.

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Self-citation

Authors: Merry, T. L., Steinberg, G. R., Lynch, G. S., & McConell, G. K.
Affiliations: The University of Melbourne (AU)
McMaster University (CA)
Exercise Physiology and Metabolism Laboratory,
Corresponding author: Merry, Troy L.
ORCID: Merry, Troy L.
Steinberg, Gregory R.
Lynch, Gordon S.
McConell, Glenn K.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2010-03
Volume: 298
Issue: 3
Pages: E577-E585
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00239.2009
OpenAlex: W2103404817
Cited by: 122
References: 57
Citations by year: 2026: 1 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 5 · 2020: 17 · 2019: 8 · 2018: 7 · 2017: 5 · 2016: 10 · 2015: 14 · 2014: 10 · 2013: 7 · 2012: 6
FWCI: 2.82
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Victoria University Research Repository (Victoria University) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
Keywords: skeletal muscle glucose uptake, muscle contraction, nitric oxide, reactive oxygen species, AMPK, AMPK-independent mechanism, AMPKα2, nitric oxide synthase, neuronal nitric oxide synthase, oxidative stress, N-acetylcysteine, L-NMMA, extensor digitorum longus, soleus muscle
MeSH terms: AMP-Activated Protein Kinase Kinases, Animals, Female, Glucose, Male, Mice, Inbred C57BL, Mice, Transgenic, Muscle Contraction, Nitric Oxide, Protein Kinases, Signal Transduction, Reactive Oxygen Species, Muscle, Skeletal, Mice

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Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK

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