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

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Merry, Troy L, Steinberg, Gregory R, Lynch, Gordon S and McConell, Glenn ORCID: 0000-0002-8572-9065 (2010) Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK. American Journal of Physiology - Endocrinology and Metabolism, 298 (3). E577-E585. ISSN 0193-1849 (print) 1522-1555 (online)

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 NG-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 Thr172 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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Item type Article
URI https://vuir.vu.edu.au/id/eprint/7007
DOI https://doi.org/10.1152/ajpendo.00239.2009
Official URL http://ajpendo.physiology.org/content/298/3/E577
Subjects Historical > Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Historical > FOR Classification > 0606 Physiology
Historical > SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Keywords ResPubID21012, ResPubID22459, nitric oxide, reactive oxygen species, exercise, metabolism, contraction, glucose uptake
Citations in Scopus 93 - View on Scopus
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