Activation by Exercise of Human Skeletal Muscle Pyruvate Dehydrogenase <i>In Vivo</i>

Ward, G. R.; Sutton, John R.; Jones, Norman L.; Toews, C. J.

doi:10.1042/cs0630087

Cited by 26 publications

(16 citation statements)

References 19 publications

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“…The exercise-induced activation of PDH a activity corresponds well with previous human studies on vastus lateralis (18,22,26,31,32). In these studies, the intensity has in general been moderate [45-55% maximal oxygen consumption (V O 2 max ) or watt max ], and only one study examined PDH a activity during intense exercise (6), where subjects performed graded 10-min sessions of exercise at 60 and 90% V O 2 max .…”

Section: Discussionmentioning

confidence: 58%

Regulation of PDH in human arm and leg muscles at rest and during intense exercise

Kiilerich

Birk²,

Damsgaard³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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To test the hypothesis that pyruvate dehydrogenase (PDH) is differentially regulated in specific human muscles, regulation of PDH was examined in triceps, deltoid, and vastus lateralis at rest and during intense exercise. To elicit considerable glycogen use, subjects performed 30 min of exhaustive arm cycling on two occasions and leg cycling exercise on a third day. Muscle biopsies were obtained from deltoid or triceps on the arm exercise days and from vastus lateralis on the leg cycling day. Resting PDH protein content and phosphorylation on PDH-E1␣ sites 1 and 2 were higher (P Յ 0.05) in vastus lateralis than in triceps and deltoid as was the activity of oxidative enzymes. Net muscle glycogen utilization was similar in vastus lateralis and triceps (Ϸ50%) but less in deltoid (likely reflecting less recruitment of deltoid), while muscle lactate accumulation was Ϸ55% higher (P Յ 0.05) in triceps than vastus lateralis. Exercise induced (P Յ 0.05) dephosphorylation of both PDH-E1␣ site 1 and site 2 in all three muscles, but it was more pronounced at PDH-E1␣ site 1 in triceps than in vastus lateralis (P Յ 0.05). The increase in activity of the active form of PDH (PDHa) after 10 min of exercise was more marked in vastus lateralis (Ϸ246%) than in triceps (Ϸ160%), but when it was related to total PDH-E1␣ protein content, no difference was evident. In conclusion, PDH protein content seems to be related to metabolic enzyme profile, rather than myosin heavy chain composition, and less PDH capacity in triceps is a likely contributing factor to higher lactate accumulation in triceps than in vastus lateralis. pyruvate dehydrogenase; pyruvate dehydrogenase activity; pyruvate dehydrogenase phosphorylation; muscle type ARM AND LEG SKELETAL MUSCLES in humans differ in their metabolic response to exercise. Examples are a larger glucose extraction in arm than in leg muscles and a markedly higher net lactate release at similar relative exercise intensities (1). Moreover, the fatty acid uptake as well as the contribution of lipids for the energy yield are less in the arms (27). Also, the action of insulin appears to be most pronounced in the arm muscles with a larger insulin-stimulated glucose uptake and a further lowering of the free fatty acid (FFA) uptake (19,27). These differences in metabolism comparing arm and leg muscles can hardly be explained by fiber type, blood flow, or oxygen delivery alone, as these variables are quite similar in the muscles of the upper and lower limbs (1). The interest in understanding especially the difference in lactate release is emphasized by lactate being a central player in both cellular and whole body metabolism (12). Training status could play a role, but even in the most well-trained endurance athletes using their arms just as much as their legs, a high dependency of carbohydrates and high lactate production are still observed in the arm muscles (8). This indicates that the difference in metabolic response to exercise between arm and leg muscles could be related to the metabolic profile of th...

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Section: Discussionmentioning

confidence: 58%

Regulation of PDH in human arm and leg muscles at rest and during intense exercise

Kiilerich

Birk²,

Damsgaard³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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“…Especially PDK has proven to be highly regulated at the mRNA level in skeletal muscle in recovery from exercise (33,35), and acute regulation of PDK4 expression has been suggested to play a role in restoring muscle glycogen stores after exercise (34). The activity of PDH in the active form (PDHa) increases in human skeletal muscle during exercise as first demonstrated by Ward et al (45) and an associated dephosphorylation of PDH-E1␣ has been shown more recently (16,17,32). The exercise-induced PDHa activation increases with increasing power output (12), and the upregulation of PDHa activity in the initial part of an exercise bout occurs concomitant with increased carbohydrate use (17,47).…”

mentioning

confidence: 79%

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

Kiilerich

Ringholm

Biensø

et al. 2011

Journal of Applied Physiology

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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 (Wmax)] 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 Յ 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 Յ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05Ͻ P Յ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1␣ protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P Յ 0.05) the activity of PDH in the active form (PDHa) and induced (P Յ 0.05) dephosphorylation of PDH-E1␣ on Ser 293 , Ser 295 and Ser 300

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“…Thus, several studies have reported a decrease in PDH activity in response to fasting and alloxan-streptozotocin-induced diabetes in rat muscle (for review, see Roche et al 2001;Sugden & Holness, 2003) and in response to a high-fat diet in human muscle (Putman et al 1993). In addition, an exercise-or contraction-induced increase in PDH activity has been demonstrated in both rat (Hennig et al 1975;Hagg et al 1976;Dohm et al 1986;Brozinick et al 1988) and human (Ward et al 1982;Putman et al 1993) muscle during exercise or contractions of £2 h duration. Determination of PDH activity during exercise of >2 h duration has not been performed until recently (see p. 224).…”

Section: Structure and Regulation Of The Pyruvate Dehydrogenase Complexmentioning

confidence: 99%

“…Possible role of pyruvate dehydrogenase kinase 4 expression in substrate utilization during exercise As mentioned earlier, several studies have previously shown that PDH activity is rapidly increased during the initial 1-2 h of exercise (Hennig et al 1975;Hagg et al 1976;Ward et al 1982;Dohm et al 1986;Brozinick et al 1988;Putman et al 1993). The finding that PDK4 transcription and mRNA content increase during prolonged exercise, together with the known switch occurring in substrate utilization in skeletal muscle during prolonged exercise, has led to the proposal that increased PDK4 expression might have an effect on PDH activity during prolonged exercise.…”

Section: Potential Transcription Factors Involved In Regulating the Pmentioning

confidence: 99%

Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise

2004

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The pyruvate dehydrogenase complex (PDC) has a key position in skeletal muscle metabolism as it represents the entry of carbohydrate-derived fuel into the mitochondria for oxidation. PDC is regulated by a phosphorylation-dephosphorylation cycle, in which the pyruvate dehydrogenase kinase (PDK) phosphorylates and inactivates the complex. PDK exists in four isoforms, of which the PDK4 isoform is predominantly expressed in skeletal and heart muscle. PDK4 transcription and PDK4 mRNA are markedly increased in human skeletal muscle during prolonged exercise and after both short-term high-intensity and prolonged low-intensity exercise. The exercise-induced transcriptional response of PDK4 is enhanced when muscle glycogen is lowered before the exercise, and intake of a low-carbohydrate high-fat diet during recovery from exercise results in increased transcription and mRNA content of PDK4 when compared with intake of a high-carbohydrate diet. The activity of pyruvate dehydrogenase (PDH) is increased during the first 2 h of low-intensity exercise, followed by a decrease towards resting levels, which is in line with the possibility that the increased PDK4 expressed influences the PDH activity already during prolonged exercise. PDK4 expression is also increased in response to fasting and a high-fat diet. Thus, increased PDK4 expression when carbohydrate availability is low seems to contribute to the sparing of carbohydrates by preventing carbohydrate oxidation. The impact of substrate availability on PDK4 expression during recovery from exercise also underlines the high metabolic priority given to replenishing muscle glycogen stores and re-establishing intracellular homeostasis after exercise. Pyruvate dehydrogenase kinase 4: Transcriptional regulation: Skeletal muscle: ExerciseOxidative phosphorylation is crucial to skeletal muscle metabolism, particularly during prolonged endurance exercise. For oxidative use, carbohydrates enter the mitochondria via the decarboxylation of pyruvate to acetyl-CoA in a reaction catalysed by the pyruvate dehydrogenase complex (PDC):This irreversible enzymic reaction plays a key role in muscle metabolism, as it represents the only entry point for carbohydrates (derived either from circulating glucose or intramuscular glycogen) into the mitochondria for complete oxidation. Thus, the PDC is positioned such that it is likely to play a key role in regulating the metabolic fate of glucose as well as overall substrate selection in skeletal muscle. Structure and regulation of the pyruvate dehydrogenase complexThe mammalian PDC is a multienzyme assembly composed of multiple copies of three catalytic enzymes (pyruvate dehydrogenase (E1); dihydrolipoamide acetyltransferase (E2); dihydrolipoamide dehydrogenase (E3)), one structural protein (E3-binding protein) and two regulatory enzymes (pyruvate dehydrogenase kinase (PDK);Abbreviations: E1, E2, E3, catalytic subunits of PDC; FKHR, forkhead homologue in rhabdomyosarcoma; PDC, pyruvate dehydrogenase complex; PDH, pyruvate dehydrogenase; PDK, pyruvate deh...

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Activation by Exercise of Human Skeletal Muscle Pyruvate Dehydrogenase In Vivo

Cited by 26 publications

References 19 publications

Regulation of PDH in human arm and leg muscles at rest and during intense exercise

Regulation of PDH in human arm and leg muscles at rest and during intense exercise

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

Transcriptional regulation of pyruvate dehydrogenase kinase 4 in skeletal muscle during and after exercise

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