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1.
IUBMB Life ; 60(3): 145-53, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18380005

ABSTRACT

Physical activity elicits physiological responses in skeletal muscle that result in a number of health benefits, in particular in disease states, such as type 2 diabetes. An acute bout of exercise/muscle contraction improves glucose homeostasis by increasing skeletal muscle glucose uptake, while chronic exercise training induces alterations in the expression of metabolic genes, such as those involved in muscle fiber type, mitochondrial biogenesis, or glucose transporter 4 (GLUT4) protein levels. A primary goal of exercise research is to elucidate the mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we briefly summarize the current literature describing the molecular signals underlying skeletal muscle responses to acute and chronic exercise. The search for possible exercise/contraction-stimulated signaling proteins involved in glucose transport, muscle fiber type, and mitochondrial biogenesis is ongoing. Further research is needed because full elucidation of exercise-mediated signaling pathways would represent a significant step toward the development of new pharmacological targets for the treatment of metabolic diseases such as type 2 diabetes.


Subject(s)
Adaptation, Physiological , Exercise , Muscle, Skeletal/physiology , Signal Transduction/physiology , AMP-Activated Protein Kinases , Calcineurin/metabolism , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , GTPase-Activating Proteins/metabolism , Glucose/metabolism , Heat-Shock Proteins , Humans , Multienzyme Complexes/metabolism , Muscle, Skeletal/cytology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Protein Kinase C/metabolism , Protein Serine-Threonine Kinases/metabolism , Transcription Factors , p38 Mitogen-Activated Protein Kinases/metabolism
2.
Diabetes ; 56(8): 2062-9, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17513699

ABSTRACT

Regular endurance exercise has profound benefits on overall health, including the prevention of obesity, cardiovascular disease, and diabetes. The objective of this study was to determine whether AMP-activated protein kinase (AMPK) mediates commonly observed adaptive responses to exercise training in skeletal muscle. Six weeks of voluntary wheel running induced a significant (P < 0.05) fiber type IIb to IIa/x shift in triceps muscle of wild-type mice. Despite similar wheel running capacities, this training-induced shift was reduced by approximately 40% in transgenic mice expressing a muscle-specific AMPKalpha2 inactive subunit. Sedentary mice carrying an AMPK-activating mutation (gamma1TG) showed a 2.6-fold increase in type IIa/x fibers but no further increase with training. To determine whether AMPK is involved in concomitant metabolic adaptations to training, we measured markers of mitochondria (citrate synthase and succinate dehydrogenase) and glucose uptake capacity (GLUT4 and hexokinase II). Mitochondrial markers increased similarly in wild-type and AMPKalpha2-inactive mice. Sedentary gamma1TG mice showed a approximately 25% increase in citrate synthase activity but no further increase with training. GLUT4 protein expression was not different in either line of transgenic mice compared with wild-type mice and tended to increase with training, although this increase was not statistically significant. Training induced a approximately 65% increase in hexokinase II protein in wild-type mice but not in AMPKalpha2-inactive mice. Hexokinase II was significantly elevated in sedentary gamma1TG mice, without an additional increase with training. AMPK is not necessary for exercise training-induced increases in mitochondrial markers, but it is essential for fiber type IIb to IIa/x transformation and increases in hexokinase II protein.


Subject(s)
Adaptation, Biological , Multienzyme Complexes/metabolism , Muscle, Skeletal/enzymology , Protein Serine-Threonine Kinases/metabolism , AMP-Activated Protein Kinases , Animals , Biomarkers/metabolism , Gene Expression Regulation, Enzymologic , Glucose Transporter Type 4/metabolism , Hexokinase/metabolism , Mice , Mice, Transgenic , Mitochondrial Proteins/metabolism , Multienzyme Complexes/genetics , Mutation/genetics , Myosin Heavy Chains/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Physical Conditioning, Animal , Protein Serine-Threonine Kinases/genetics , Protein Subunits/genetics , Protein Subunits/metabolism , Trans-Activators/metabolism , Transcription Factors
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