Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest.

To test the hypothesis that physical inactivity impairs the exercise-induced modulation of pyruvate dehydrogenase (PDH), six healthy normally physically active male subjects completed 7 days of bed rest. Before and immediately after the bed rest, the subjects completed an oral glucose tolerance test (OGTT) and a one-legged knee extensor exercise bout [45 min at 60% maximal load (W(max))] with muscle biopsies obtained from vastus lateralis before, immediately after exercise, and at 3 h of recovery. Blood samples were taken from the femoral vein and artery before and after 40 min of exercise. Glucose intake elicited a larger (P ≤ 0.05) insulin response after bed rest than before, indicating glucose intolerance. There were no differences in lactate release/uptake across the exercising muscle before and after bed rest, but glucose uptake after 40 min of exercise was larger (P ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced (P ≤ 0.05) dephosphorylation of PDH-E1α on Ser²⁹³, Ser²⁹⁵ and Ser³⁰⁰, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.

[1]  O. H. Lowry,et al.  A Flexible System of Enzymatic Analysis , 2012 .

[2]  F. Booth,et al.  Muscle Plasticity: Energy Demand and Supply Processes , 2011 .

[3]  D. Hardie,et al.  PGC-1alpha increases PDH content but does not change acute PDH regulation in mouse skeletal muscle. , 2010, American journal of physiology. Regulatory, integrative and comparative physiology.

[4]  B. Pedersen,et al.  A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity. , 2010, Journal of applied physiology.

[5]  B. Saltin,et al.  Low Muscle Glycogen and Elevated Plasma Free Fatty Acid Modify but Do Not Prevent Exercise-Induced PDH Activation in Human Skeletal Muscle , 2009, Diabetes.

[6]  A. Bonen,et al.  High-intensity aerobic interval training increases fat and carbohydrate metabolic capacities in human skeletal muscle. , 2008, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[7]  B. Pedersen,et al.  Metabolic responses to reduced daily steps in healthy nonexercising men. , 2008, JAMA.

[8]  H. Pilegaard,et al.  Regulation of PDH in human arm and leg muscles at rest and during intense exercise. , 2008, American journal of physiology. Endocrinology and metabolism.

[9]  J. Wojtaszewski,et al.  Effects of Endurance Exercise Training on Insulin Signaling in Human Skeletal Muscle , 2007, Diabetes.

[10]  P. Neufer,et al.  PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion. , 2006, Diabetes.

[11]  B. Saltin,et al.  Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids. , 2006, Journal of applied physiology.

[12]  P. Neufer,et al.  Gene expression in human skeletal muscle: alternative normalization method and effect of repeated biopsies , 2005, European Journal of Applied Physiology.

[13]  P. Neufer,et al.  Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. , 2005, Metabolism: clinical and experimental.

[14]  D. Constantin-Teodosiu,et al.  Muscle pyruvate availability can limit the flux, but not activation, of the pyruvate dehydrogenase complex during submaximal exercise in humans , 2004, The Journal of physiology.

[15]  M. Gibala,et al.  Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise. , 2004, Journal of applied physiology.

[16]  L. Spriet,et al.  Rapid upregulation of pyruvate dehydrogenase kinase activity in human skeletal muscle during prolonged exercise. , 2004, Journal of applied physiology.

[17]  G. Heigenhauser,et al.  Effects of aerobic training on pyruvate dehydrogenase and pyruvate dehydrogenase kinase in human skeletal muscle , 2004, The Journal of physiology.

[18]  Y. Hellsten,et al.  Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle , 2004, The Journal of physiology.

[19]  P. Neufer,et al.  Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise , 2004, The Proceedings of the Nutrition Society.

[20]  J. Bülow,et al.  Regional Fat Metabolism in Human Splanchnic and Adipose Tissues; The Effect of Exercise , 2002, The Journal of physiology.

[21]  L. Spriet,et al.  Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of moderate exercise in man , 2002, The Journal of physiology.

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

[23]  Robert A. Harris,et al.  Regulation of the activity of the pyruvate dehydrogenase complex. , 2002, Advances in enzyme regulation.

[24]  K. M. Popov,et al.  Regulation of pyruvate dehydrogenase activity through phosphorylation at multiple sites. , 2001, The Biochemical journal.

[25]  L. Korotchkina,et al.  Probing the Mechanism of Inactivation of Human Pyruvate Dehydrogenase by Phosphorylation of Three Sites* , 2001, The Journal of Biological Chemistry.

[26]  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.

[27]  S. Gordon,et al.  Waging war on modern chronic diseases: primary prevention through exercise biology , 2000, Journal of applied physiology.

[28]  G. Heigenhauser,et al.  Pyruvate overrides inhibition of PDH during exercise after a low-carbohydrate diet. , 2000, American journal of physiology. Endocrinology and metabolism.

[29]  R. A. Howlett,et al.  Regulation of skeletal muscle glycogen phosphorylase and PDH at varying exercise power outputs. , 1998, The American journal of physiology.

[30]  I. Macdonald,et al.  Regulation of skeletal muscle carbohydrate oxidation during steady-state contraction. , 1998, American journal of physiology. Regulatory, integrative and comparative physiology.

[31]  G. Rådegran Ultrasound Doppler estimates of femoral artery blood flow during dynamic knee extensor exercise in humans. , 1997, Journal of applied physiology.

[32]  Robert A. Harris,et al.  Alpha-Keto Acid Dehydrogenase Complexes , 1996, MCBU Molecular and Cell Biology Updates.

[33]  L. Rowell,et al.  Exercise : regulation and integration of multiple systems , 1996 .

[34]  R. McKelvie,et al.  Pyruvate dehydrogenase activity and acetyl group accumulation during exercise after different diets. , 1993, The American journal of physiology.

[35]  B. Saltin,et al.  Skeletal muscle substrate utilization during submaximal exercise in man: effect of endurance training. , 1993, The Journal of physiology.

[36]  B. Saltin,et al.  Free fatty acids and exercise. , 1993, The American journal of clinical nutrition.

[37]  D. Constantin-Teodosiu,et al.  A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue. , 1991, Analytical biochemistry.

[38]  D. Constantin-Teodosiu,et al.  Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle. , 1990, Analytical biochemistry.

[39]  B. Gu,et al.  Estimate of the escape time of resonant tunneling electrons from a quantum well in double‐barrier heterostructures , 1989 .

[40]  F. Dela,et al.  Effect of 7 days of bed rest on dose-response relation between plasma glucose and insulin secretion. , 1989, The American journal of physiology.

[41]  H. Galbo,et al.  Effects of acute exercise and detraining on insulin action in trained men. , 1989, Journal of applied physiology.

[42]  L. Mandarino,et al.  Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism. , 1987, The Journal of clinical investigation.

[43]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[44]  N. Jones,et al.  Activation of human muscle pyruvate dehydrogenase with activity and immobilization. , 1986, Clinical science.

[45]  B. Saltin,et al.  Maximal perfusion of skeletal muscle in man. , 1985, The Journal of physiology.

[46]  N. Jones,et al.  Activation by exercise of human skeletal muscle pyruvate dehydrogenase in vivo. , 1982, Clinical science.

[47]  J. Henriksson,et al.  Time course of changes in human skeletal muscle succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen uptake with physical activity and inactivity. , 1977, Acta physiologica Scandinavica.

[48]  De Vries,et al.  Response to Exercise After Bed Rest and After Training , 1969 .

[49]  L. Reed,et al.  Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. , 1969, Proceedings of the National Academy of Sciences of the United States of America.

[50]  B. Saltin,et al.  Physiological Analysis of Middle‐Aged and Old Former Athletes: Comparison with Still Active Athletes of the Same Ages , 1968, Circulation.

[51]  J. Bergstrom MUSCLE ELECTROLYTES IN MAN DETERMINED BY NEUTRON ACTIVATION ANALYSIS ON NEEDLE BIOPSY SPECIMENS , 1962 .