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Updated: Jun 17, 2026

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
08:01

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice

Published on: May 16, 2021

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

Troy L Merry1, Gregory R Steinberg, Gordon S Lynch

  • 1Dept. of Physiology, Univ. of Melbourne, Victoria, Australia. t.merry@pgrad.unimelb.edu.au

American Journal of Physiology. Endocrinology and Metabolism
|December 17, 2009
PubMed

Insights

Reactive oxygen species (ROS) and nitric oxide (NO) regulate skeletal muscle glucose uptake during exercise independently of AMP-activated protein kinase (AMPK). This suggests novel therapeutic targets for metabolic disorders.

Area of Science:

  • Skeletal Muscle Physiology
  • Metabolic Regulation
  • Cellular Signaling

Background:

  • Reactive oxygen species (ROS) and nitric oxide (NO) are known regulators of skeletal muscle glucose uptake during contraction.
  • Existing evidence suggests these molecules interact with AMP-activated protein kinase (AMPK) in this process.
  • The precise mechanism, particularly its independence from AMPK, requires further investigation.

Purpose of the Study:

  • To test the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.
  • To elucidate the role of ROS and NO in contraction-stimulated glucose uptake in different skeletal muscle types.

Main Methods:

  • Isolated extensor digitorum longus (EDL) and soleus muscles from wild-type (WT) and muscle-specific kinase dead AMPKalpha2 isoform (AMPK-KD) mice were used.
  • Muscles were stimulated to contract, and glucose uptake was measured.
  • The effects of the antioxidant N-acetyl-l-cysteine (NAC) and the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA) were assessed.

Main Results:

  • Contraction increased glucose uptake in both WT and AMPK-KD muscles, indicating an AMPK-independent effect.
  • In EDL muscles, NAC and l-NMMA attenuated contraction-stimulated glucose uptake, while in soleus muscles, only NAC had a significant effect.
  • Contraction increased AMPKalpha Thr(172) phosphorylation in WT but not AMPK-KD muscles, and this was unaffected by NAC or l-NMMA.

Conclusions:

  • ROS and NO play a significant role in regulating skeletal muscle glucose uptake during contraction through an AMPK-independent pathway.
  • The contribution of NO appears to be muscle-specific, potentially due to varying NOS isoform expression (e.g., lower in soleus).
  • These findings highlight ROS and NO as critical, AMPK-independent mediators of exercise-induced glucose uptake in skeletal muscle.

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