Cited by 126Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismMuscle Physiology and Disorders

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EXERCISE AND SKELETAL MUSCLE GLUCOSE TRANSPORTER 4 EXPRESSION: MOLECULAR MECHANISMS

McGee, Sean L, Hargreaves, Mark·2006·Clinical and Experimental Pharmacology and Physiology

DOI 10.1111/j.1440-1681.2006.04362.x

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Abstract

1. Skeletal muscle is a highly plastic tissue that has a remarkable ability to adapt to external demands, such as exercise. Many of these adaptations can be explained by changes in skeletal muscle gene expression. A single bout of exercise is sufficient to induce the expression of some metabolic genes. We have focused our attention on the regulation of glucose transporter isoform 4 (GLUT-4) expression in human skeletal muscle. 2. Glucose transporter isoform 4 gene expression is increased immediately following a single bout of exercise, and the GLUT-4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) transcription factors are required for this response. Glucose transporter isoform enhancer factor and MEF2 DNA binding activities are increased following exercise, and the molecular mechanisms regulating MEF2 in exercising human skeletal muscle have also been examined. 3. These studies find possible roles for histone deacetylase 5 (HDAC5), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and p38 mitogen-activated protein kinase (MAPK) in regulating MEF2 through a series of complex interactions potentially involving MEF2 repression, coactivation and phosphorylation. 4. Given that MEF2 is a transcription factor required for many exercise responsive genes, it is possible that these mechanisms are responsible for regulating the expression of a variety of metabolic genes during exercise. These mechanisms could also provide targets for the treatment and management of metabolic disease states, such as obesity and type 2 diabetes, which are characterized by mitochondrial dysfunction and insulin resistance in skeletal muscle.

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Authors: McGee, S. L., & Hargreaves, M.
Affiliations: The University of Melbourne (AU)
Corresponding author: Hargreaves, Mark
ORCID: McGee, Sean L
Hargreaves, Mark
Venue: Clinical and Experimental Pharmacology and Physiology
Publisher: Wiley
Published: 2006-03-16
Volume: 33
Issue: 4
Pages: 395-399
ISSN: 0305-1870 (ISSN-L)
1440-1681
DOI: 10.1111/j.1440-1681.2006.04362.x
OpenAlex: W2143945526
Cited by: 126
References: 47
Citations by year: 2026: 2 · 2025: 8 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 12 · 2012: 11
FWCI: 0.64
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Clinical and Experimental Pharmacology and Physiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords: physical activity, skeletal muscle, GLUT4, glucose transporter 4, gene expression, MEF2, transcription factors, HDAC5, AMPK, PGC-1α, p38 MAPK, muscle plasticity, insulin resistance, type 2 diabetes, obesity, mitochondrial dysfunction
MeSH terms: Gene Expression Regulation, Histone Deacetylases, Humans, Phosphorylation, Exercise, Myogenic Regulatory Factors, Muscle, Skeletal, MADS Domain Proteins, Glucose Transporter Type 4, MEF2 Transcription Factors

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EXERCISE AND SKELETAL MUSCLE GLUCOSE TRANSPORTER 4 EXPRESSION: MOLECULAR MECHANISMS

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