Effect of carbohydrate ingestion on exercise-induced alterations in metabolic gene expression.

Skeletal muscle possesses a high degree of plasticity and can adapt to both the physical and metabolic challenges that it faces. An acute bout of exercise is sufficient to induce the expression of a variety of metabolic genes, such as GLUT4, pyruvate dehydrogenase kinase 4 (PDK-4), uncoupling protein-3 (UCP3), and peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1). Reducing muscle glycogen levels before exercise potentiates the effect of exercise on many genes. Similarly, altered substrate availability induces transcription of many of these genes. The purpose of this study was to determine whether glucose ingestion attenuates the exercise-induced increase in a variety of exercise-responsive genes. Six male subjects (28 +/- 7 yr; 83 +/- 3 kg; peak pulmonary oxygen uptake = 46 +/- 6 ml.kg(-1).min(-1)) performed 60 min of cycling at 74 +/- 2% of peak pulmonary oxygen uptake on two separate occasions. On one occasion, subjects ingested a 6% carbohydrate drink. On the other occasion, subjects ingested an equal volume of a sweet placebo. Muscle samples were obtained from vastus lateralis at rest, immediately after exercise, and 3 h after exercise. PDK-4, UCP3, PGC-1, and GLUT4 mRNA levels were measured on these samples using real-time RT-PCR. Glucose ingestion attenuated (P < 0.05) the exercise-induced increase in PDK-4 and UCP3 mRNA. A similar trend (P = 0.09) was observed for GLUT4 mRNA. In contrast, PGC-1 mRNA increased following exercise to the same extent in both conditions. These data suggest that glucose availability can modulate the effect of exercise on metabolic gene expression.

[1]  F. N. Lee,et al.  Insulin suppresses PDK-4 expression in skeletal muscle independently of plasma FFA. , 2004, American journal of physiology. Endocrinology and metabolism.

[2]  E. Ojuka.  Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle , 2004, The Proceedings of the Nutrition Society.

[3]  D. Cameron-Smith,et al.  Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting. , 2004, Journal of applied physiology.

[4]  J. Ivy,et al.  Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle. , 2004, Journal of applied physiology.

[5]  P. Schrauwen,et al.  Human uncoupling protein-3 and obesity: an update. , 2003, Obesity research.

[6]  T. Furuyama,et al.  Forkhead transcription factor FOXO1 (FKHR)-dependent induction of PDK4 gene expression in skeletal muscle during energy deprivation. , 2003, The Biochemical journal.

[7]  M. Suwa,et al.  Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles. , 2003, Journal of applied physiology.

[8]  Jiandie D. Lin,et al.  An autoregulatory loop controls peroxisome proliferator-activated receptor γ coactivator 1α expression in muscle , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Holloszy,et al.  Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[10]  L. Nolte,et al.  Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC‐1 , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  Jiandie D. Lin,et al.  Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres , 2002, Nature.

[12]  D. Cameron-Smith,et al.  Fasting activates the gene expression of UCP3 independent of genes necessary for lipid transport and oxidation in skeletal muscle. , 2002, Biochemical and biophysical research communications.

[13]  P. Neufer,et al.  Influence of pre‐exercise muscle glycogen content on exercise‐induced transcriptional regulation of metabolic genes , 2002, The Journal of physiology.

[14]  Robert A. Harris,et al.  Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. , 2002, Diabetes.

[15]  H. Itoh,et al.  Up-regulation of uncoupling protein 3 gene expression by fatty acids and agonists for PPARs in L6 myotubes. , 2001, Endocrinology.

[16]  R. Harris,et al.  Muscle fiber type comparison of PDH kinase activity and isoform expression in fed and fasted rats. , 2001, American journal of physiology. Regulatory, integrative and comparative physiology.

[17]  P. Neufer,et al.  Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise. , 2000, American journal of physiology. Endocrinology and metabolism.

[18]  R. Darwich,et al.  Effect of fill-pulse parameters on deep-level transient spectroscopy peaks in highly doped p-type InP , 2000 .

[19]  D. Cameron-Smith,et al.  Effects of exercise on GLUT-4 and glycogenin gene expression in human skeletal muscle. , 2000, Journal of applied physiology.

[20]  Z. Ding,et al.  Effect of carbohydrate supplementation on postexercise GLUT-4 protein expression in skeletal muscle. , 1999, Journal of applied physiology.

[21]  P. Cohen,et al.  Phosphorylation of the Transcription Factor Forkhead Family Member FKHR by Protein Kinase B* , 1999, The Journal of Biological Chemistry.

[22]  D. Cooke,et al.  The Transcription Factor Nuclear Factor I Mediates Repression of the GLUT4 Promoter by Insulin* , 1999, The Journal of Biological Chemistry.

[23]  R. Seeley,et al.  Elevated Free Fatty Acids Induce Uncoupling Protein 3 Expression in Muscle: A Potential Explanation for the Effect of Fasting , 1998, Diabetes.

[24]  P. Neufer,et al.  Exercise induces a transient increase in transcription of the GLUT-4 gene in skeletal muscle. , 1993, The American journal of physiology.

[25]  P. Neufer,et al.  Transcriptional regulation of the gene for glucose transporter GLUT4 in skeletal muscle. Effects of diabetes and fasting. , 1993, The Journal of biological chemistry.

[26]  H. Vestergaard,et al.  Expression of the major insulin regulatable glucose transporter (GLUT4) in skeletal muscle of noninsulin-dependent diabetic patients and healthy subjects before and after insulin infusion. , 1993, The Journal of clinical endocrinology and metabolism.

[27]  R. Printz,et al.  The Effects of Hyperinsulinemia and Hyperglycemia on GLUT4 and Hexokinase II mRNA and Protein in Rat Skeletal Muscle and Adipose Tissue , 1993, Diabetes.

[28]  G. Bell,et al.  Regulation of glucose transporter messenger RNA in insulin-deficient states , 1989, Nature.

[29]  J. Passonneau,et al.  A comparison of three methods of glycogen measurement in tissues. , 1974, Analytical biochemistry.

[30]  Jiandie D. Lin,et al.  An autoregulatory loop controls peroxisome proliferator-activated receptor gamma coactivator 1alpha expression in muscle. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Jiandie D. Lin,et al.  Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. , 2002, Nature.

[32]  A. Russell,et al.  Effect of acute exercise on uncoupling protein 3 is a fat metabolism-mediated effect. , 2002, American journal of physiology. Endocrinology and metabolism.

[33]  B. Lowell,et al.  Regulation of skeletal muscle UCP-2 and UCP-3 gene expression by exercise and denervation. , 1999, American journal of physiology. Endocrinology and metabolism.

[34]  K. M. Popov,et al.  Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. , 1998, The Biochemical journal.

[35]  F. Assimacopoulos-Jeannet,et al.  Glucose transporters: structure, function, and regulation. , 1991, Biochimie.

[36]  W. Evans,et al.  Suction applied to a muscle biopsy maximizes sample size. , 1982, Medicine and science in sports and exercise.