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Cited by 709Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismMuscle Physiology and Disorders

Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle

Winder, W. W., Holmes, B. F., Rubink, D. S., Jensen, E. B., Chen, M., Holloszy, J. O.·2000·Journal of Applied Physiology
DOI 10.1152/jappl.2000.88.6.2219
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Abstract

Muscle contraction causes an increase in activity of 5′-AMP-activated protein kinase (AMPK). This study was designed to determine whether chronic chemical activation of AMPK will increase mitochondrial enzymes, GLUT-4, and hexokinase in different types of skeletal muscle of resting rats. In acute studies, rats were subcutaneously injected with either 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; 1 mg/g body wt) in 0.9% NaCl or with 0.9% NaCl alone and were then anesthetized for collection and freezing of tissues. AMPK activity increased in the superficial, white region of the quadriceps and in soleus muscles but not in the deep, red region of the quadriceps muscle. Acetyl-CoA carboxylase (ACC) activity, a target for AMPK, decreased in all three muscle types in response to AICAR injection but was lowest in the white quadriceps. In rats given daily, 1 mg/g body wt, subcutaneous injections of AICAR for 4 wk, activities of citrate synthase, succinate dehydrogenase, and malate dehydrogenase were increased in white quadriceps and soleus but not in red quadriceps. Cytochrome c and δ-aminolevulinic acid synthase levels were increased in white, but not red, quadriceps. Carnitine palmitoyl-transferase and hydroxy-acyl-CoA dehydrogenase were not significantly increased. Hexokinase was markedly increased in all three muscles, and GLUT-4 was increased in red and white quadriceps. These results suggest that chronic AMPK activation may mediate the effects of muscle contraction on some, but not all, biochemical adaptations of muscle to endurance exercise training.

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Crossref · 10.1152/jappl.2000.88.6.2219

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  • Long-term suppression of AMPK could reduce the increase in CS activity and reduce muscle glycogen accumulation.

    “Glucose ingestion can attenuate the rise in AMPK [42], and long-term suppression of AMPK in turn could reduce the increase in CS activity [43] and reduce muscle glycogen accumulation [44], two common markers of training adaptation.”

    From Periodized Nutrition for Athletes (2017) · cites this paper as [43]

  • Pharmacologic activation of AMPK increases PGC-1α, favoring mitochondrial biogenesis.

    “Pharmacologic activation of AMPK, like resveratrol, increases PGC-1α, favoring mitochondrial biogenesis (28, 329).”

    From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [329]

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Authors
Winder, W. W., Holmes, B. F., Rubink, D. S., Jensen, E. B., Chen, M., & Holloszy, J. O.
Affiliations
Brigham Young University (US)
Venue
Journal of Applied Physiology
Publisher
American Physiological Society
Published
2000-06-01
Volume
88
Issue
6
Pages
2219-2226
ISSN
  • 0161-7567 (ISSN-L)
  • 8750-7587
  • 1522-1601
DOI
10.1152/jappl.2000.88.6.2219
OpenAlex
W2176414067
Cited by
709
References
42
Citations by year
2026: 3 · 2025: 5 · 2024: 10 · 2023: 4 · 2022: 16 · 2021: 19 · 2020: 24 · 2019: 23 · 2018: 22 · 2017: 25 · 2016: 27 · 2015: 35 · 2014: 47 · 2013: 53 · 2012: 45
FWCI
8.07
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Applied Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-14138, AR-00425)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
AMPK, AICAR, skeletal muscle, mitochondrial enzymes, muscle fiber type, soleus muscle, acetyl-CoA carboxylase, GLUT4, hexokinase, citrate synthase, delta-aminolevulinic acid synthase, cytochrome c, endurance training, muscle contraction, metabolic adaptation
MeSH terms
Adaptation, Physiological, Adenosine Monophosphate, Aminoimidazole Carboxamide, Animals, Enzyme Activation, Hexokinase, Leg, Male, Mitochondria, Muscle, Monosaccharide Transport Proteins, Muscle Proteins, Protein Kinases, Ribonucleotides, Time Factors, Rats, Sprague-Dawley, Muscle, Skeletal, Glucose Transporter Type 4, Rats

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