Enhanced pyruvate dehydrogenase activity does not affect muscle O2uptake at onset of intense exercise in humans

2002 ◽  
Vol 282 (1) ◽  
pp. R273-R280 ◽  
Author(s):  
Jens Bangsbo ◽  
Martin J. Gibala ◽  
Peter Krustrup ◽  
José González-Alonso ◽  
Bengt Saltin
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Initial Phase ◽  
Vastus Lateralis ◽  
Active Form ◽  
Lactate Production ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Experimental Conditions ◽  
Very High ◽  
Exercise In Humans

It has been proposed that the activation state of pyruvate dehydrogenase (PDH) may influence the rate of skeletal muscle O2uptake during the initial phase of exercise; however, this has not been directly tested in humans. To remedy this, we used dichloroacetate (DCA) infusion to increase the active form of PDH (PDHa) and, subsequently, measured leg O2uptake and markers of anaerobic ATP provision during conditions of intense dynamic exercise, when the rate of muscle O2uptake would be very high. Six subjects performed brief bouts of one-legged knee-extensor exercise at ∼110% of thigh peak O2uptake (65.3 ± 3.7 W) on several occasions: under noninfused control (Con) and DCA-supplemented conditions. Needle biopsy samples from the vastus lateralis muscle were obtained at rest and after 5 s, 15 s, and 3 min of exercise during both experimental conditions. In addition, thigh blood flow and femoral arteriovenous differences for O2and lactate were measured repeatedly during the 3-min work bouts (Con and DCA) to calculate thigh O2uptake and lactate release. After DCA administration, PDHawas four- to eightfold higher ( P < 0.05) than Con at rest, and PDHaremained ∼130% and 100% higher ( P< 0.05) after 5 and 15 s of exercise, respectively. There was no difference between trials after 3 min. Despite the marked difference in PDHabetween trials at rest and during the initial phase of exercise, thigh O2uptake was the same. In addition, muscle phosphocreatine utilization and lactate production were similar after 5 s, 15 s, and 3 min of exercise in DCA and Con. The present findings demonstrate that increasing PDHadoes not alter muscle O2uptake and anaerobic ATP provision during the initial phase of intense dynamic knee-extensor exercise in humans.

Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans

1995 ◽  
Vol 269 (3) ◽  
pp. E458-E468 ◽  
Author(s):  
C. T. Putman ◽  
N. L. Jones ◽  
L. C. Lands ◽  
T. M. Bragg ◽  
M. G. Hollidge-Horvat ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Maximal Exercise ◽  
Vastus Lateralis ◽  
Active Form ◽  
Lactate Production ◽  
Glycolytic Flux ◽  
Muscle Lactate ◽  
Mitochondrial Oxidation ◽  
Exercise In Humans

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.

Activation by Exercise of Human Skeletal Muscle Pyruvate Dehydrogenase In Vivo

1982 ◽  
Vol 63 (1) ◽  
pp. 87-92 ◽  
Author(s):  
G. R. Ward ◽  
J. R. Sutton ◽  
N. L. Jones ◽  
C. J. Toews
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Maximal Exercise ◽  
Intermittent Exercise ◽  
Vastus Lateralis ◽  
Active Form ◽  
Isometric Exercise ◽  
Vastus Lateralis Muscle ◽  
Glycogen Depletion ◽  
Muscle Lactate

1. The activity of pyruvate dehydrogenase in its active and inactive forms was measured in biopsy samples obtained from the vastus lateralis muscle of healthy subjects before and after exercise. 2. At rest, 40 ± 4% (mean ± sem) of the enzyme was in the active form. 3. After progressive aerobic exercise to exhaustion (n = 5), 88 ± 2·3% was in the active form. 4. After intermittent supramaximal short-term exercise (1 min exercise, 3 min rest) to exhaustion (n = 6), 60 ± 2·2% was in the active form. 5. After isometric maximal exercise of 65 ± 3·6 s duration (n = 3), only 39 ± 1% of the enzyme was in the active form. 6. Muscle glycogen depletion was greatest with intermittent exercise and least with isometric maximal exercise; in contrast, the increase in muscle lactate was least with progressive exercise (1·3 to 9·4 μmol/g), intermediate in intermittent maximal exercise (1·2 to 13·1 μmol/g) and greatest after isometric exercise (1·8 to 17·6 μmol/g). There were no significant differences between the three studies in the changes in lactate/pyruvate ratios. 7. In three subjects who exercised with one leg, activation of the enzyme was twice as great in the exercised as in the inactive leg. 8. The ratio of active to total enzyme in biopsies of resting muscle was greater in four well-trained athletes than in four untrained control subjects (70% compared with 41% respectively). 9. The activation of pyruvate dehydrogenase appears to play an important part in regulating the use of glycogen and glucose during exercise in man.

Intent-Related Differences in Surface EMG of Maximum Eccentric and Concentric Contractions

2003 ◽  
Vol 19 (2) ◽  
pp. 99-105 ◽  
Author(s):  
Mark D. Grabiner ◽  
Tammy M. Owings
Keyword(s):  
Muscle Activation ◽  
Vastus Lateralis ◽  
Knee Extensor ◽  
Eccentric Contraction ◽  
Surface Emg ◽  
Vastus Lateralis Muscle ◽  
Concentric Contractions ◽  
Concentric Contraction ◽  
Contraction Condition ◽  
The Difference

For this study it was hypothesized that when participants intended to perform a maximum voluntary concentric (or eccentric) contraction but had an eccentric (or concentric) contraction imposed upon them, the initial EMG measured during the isometric phase preceding the onset of the dynamometer motion would reflect the intended contraction condition. The surface EMG of the vastus lateralis muscle was measured in 24 participants performing isokinetic concentric and eccentric maximum voluntary knee extensor contractions. The contractions were initiated from rest and from the same knee flexion angle and required the same level of external force to trigger the onset of dynamometer motion. Vastus lateralis EMG were quantified during the isometric phase preceding the onset of the dynamometer motion. When participants intended to perform a concentric contraction but had an eccentric contraction imposed upon them, the initial EMG resembled that of a concentric contraction. When they intended to perform an eccentric contraction but had a concentric contraction imposed upon them, the initial EMG resembled that of an eccentric contraction. Overall, the difference between concentric and eccentric contractions observed during the period of theinitialmuscle activation implies that descending signals include information that distinguishes between eccentric and concentric contractions.

scholarly journals Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans

2016 ◽  
Vol 120 (11) ◽  
pp. 1355-1363 ◽  
Author(s):  
Sean A. Newsom ◽  
Joseph T. Brozinick ◽  
Katja Kiseljak-Vassiliades ◽  
Allison N. Strauss ◽  
Samantha D. Bacon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Acute Exercise ◽  
Contractile Function ◽  
Vastus Lateralis ◽  
Mass Spectrometry Analysis ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Exercise In Humans

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D ( P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH ( P < 0.05), tended to be elevated in OB vs. ATH ( P = 0.07), and was inversely related to insulin sensitivity among the entire cohort ( r = −0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio.

Calpain-3 is autolyzed and hence activated in human skeletal muscle 24 h following a single bout of eccentric exercise

2007 ◽  
Vol 103 (3) ◽  
pp. 926-931 ◽  
Author(s):  
Robyn M. Murphy ◽  
Craig A. Goodman ◽  
Michael J. McKenna ◽  
Jason Bennie ◽  
Murray Leikis ◽  
...  
Keyword(s):  
Eccentric Exercise ◽  
Human Subjects ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Healthy Human ◽  
Calpain 3 ◽  
Torque Measurements

The function and normal regulation of calpain-3, a muscle-specific Ca2+-dependent protease, is uncertain, although its absence leads to limb-girdle muscular dystrophy type 2A. This study examined the effect of eccentric exercise on calpain-3 autolytic activation, because such exercise is known to damage sarcomeric structures and to trigger adaptive changes that help prevent such damage on subsequent exercise. Six healthy human subjects performed a 30-min bout of one-legged, eccentric, knee extensor exercise. Torque measurements, vastus lateralis muscle biopsies, and venous blood samples were taken before and up to 7 days following the exercise. Peak isometric muscle torque was depressed immediately and at 3 h postexercise and recovered by 24 h, and serum creatine kinase concentration peaked at 24 h postexercise. The amount of autolyzed calpain-3 was unchanged immediately and 3 h after exercise, but increased markedly (from ∼16% to ∼35% of total) 24 h after the exercise, and returned to preexercise levels within 7 days. In contrast, the eccentric exercise produced little autolytic activation of the ubiquitous Ca2+-activated protease, μ-calpain. Eccentric exercise is the first physiological circumstance shown to result in calpain-3 activation in vivo.

The effects of osteoarthritis and age on skeletal muscle strength, Na+-K+-ATPase content, gene and isoform expression

2013 ◽  
Vol 115 (10) ◽  
pp. 1443-1449 ◽  
Author(s):  
Ben D. Perry ◽  
Pazit Levinger ◽  
Fabio R. Serpiello ◽  
Marissa K. Caldow ◽  
David Cameron-Smith ◽  
...  
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Ion Homeostasis ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Knee Oa ◽  
Or Gene ◽  
Older Populations

Knee osteoarthritis (OA) is a debilitating disorder prevalent in older populations that is accompanied by declines in muscle mass, strength, and physical activity. In skeletal muscle, the Na+-K+ pump (NKA) is pivotal in ion homeostasis and excitability and is modulated by disuse and exercise training. This study examined the effects of OA and aging on muscle NKA in 36 older adults (range 55–81 yr), including 19 with OA (69.9 ± 6.5 yr, mean ± SD) and 17 asymptomatic controls (CON, 66.8 ± 6.4 yr). Participants completed knee extensor strength testing and a physical activity questionnaire. A vastus lateralis muscle biopsy was analyzed for NKA content ([3H]ouabain binding sites), α1–3- and β1–3-isoform protein abundance (immunoblotting), and mRNA (real-time RT-PCR). The association between age and NKA content was investigated within the OA and CON groups and in pooled data. The NKA content was also contrasted between subgroups below and above the median age of 68.5 yr. OA had lower strength (−40.8%, P = 0.005), but higher NKA α2- (∼34%, P = 0.006) and α3-protein (100%, P = 0.016) abundance than CON and performed more incidental physical activity ( P = 0.035). No differences were found between groups for NKA content, abundance of other NKA isoforms, or gene expression. There was a negative correlation between age and NKA content within OA ( r = −0.63, P = 0.03) and with both groups combined ( r = −0.47, P = 0.038). The NKA content was 25.5% lower in the older (69–81 yr) than in the younger (55–68 yr) subgroup. Hence older age, but not knee OA, was related to lowered muscle NKA content in older adults.

Muscle interstitial glucose and lactate levels during dynamic exercise in humans determined by microdialysis

1999 ◽  
Vol 87 (4) ◽  
pp. 1483-1490 ◽  
Author(s):  
Dave A. MacLean ◽  
Jens Bangsbo ◽  
Bengt Saltin
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Lactate Concentration ◽  
Reference Method ◽  
Vastus Lateralis Muscle ◽  
Glucose Levels ◽  
Interstitial Glucose ◽  
Lactate Levels ◽  
Exercise In Humans ◽  
Venous Plasma

The purpose of the present study was to use the microdialysis technique to determine skeletal muscle interstitial glucose and lactate concentrations during dynamic incremental exercise in humans. Microdialysis probes were inserted into the vastus lateralis muscle, and subjects performed knee extensor exercise at workloads of 10, 20, 30, 40, and 50 W. The in vivo probe recoveries determined at rest by the internal reference method for glucose and lactate were 28.7 ± 2.5 and 32.0 ± 2.7%, respectively. As exercise intensity increased, probe recovery also increased, and at the highest workload probe recovery for glucose (61.0 ± 3.9%) and lactate (66.3 ± 3.6%) had more than doubled. At rest the interstitial glucose concentration (3.5 ± 0.2 mM) was lower than both the arterial (5.6 ± 0.2 mM) and venous (5.3 ± 0.3 mM) plasma water glucose levels. The interstitial glucose levels remained lower ( P < 0.05) than the arterial and venous plasma water glucose concentrations during exercise at all intensities and at 10, 20, 30, and 50 W, respectively. At rest the interstitial lactate concentration (2.5 ± 0.2 mM) was higher ( P < 0.05) than both the arterial (0.9 ± 0.2 mM) and venous (1.1 ± 0.2 mM) plasma water lactate levels. This relationship was maintained ( P < 0.05) during exercise at workloads of 10, 20, and 30 W. These data suggest that interstitial glucose delivery at rest is flow limited and that during exercise changes in the interstitial concentrations of glucose and lactate mirror the changes observed in the venous plasma water compartments. Furthermore, skeletal muscle contraction results in an increase in the diffusion coefficient of glucose and lactate within the interstitial space as reflected by an elevation in probe recovery during exercise.

Exercise-induced translocation of Na+-K+ pump subunits to the plasma membrane in human skeletal muscle

2000 ◽  
Vol 278 (4) ◽  
pp. R1107-R1110 ◽  
Author(s):  
Carsten Juel ◽  
Jens Jung Nielsen ◽  
Jens Bangsbo
Keyword(s):  
Human Subjects ◽  
Vastus Lateralis ◽  
Knee Extensor ◽  
Vastus Lateralis Muscle ◽  
Biopsy Material ◽  
Exercise Time ◽  
Fatigue Exercise ◽  
Vesicular Membrane ◽  
Exercise Induced ◽  
Short Time

Six human subjects performed one-legged knee extensor exercise (90 ± 4 W) until fatigue (exercise time 4.6 ± 0.8 min). Needle biopsies were obtained from vastus lateralis muscle before and immediately after exercise. Production of giant sarcolemmal vesicles from the biopsy material was used as a membrane purification procedure, and Na+-K+ pump α- and β-subunits were quantified by Western blotting. Exercise significantly increased ( P < 0.05) the vesicular membrane content of the α2-, total α-, and β1-subunits by 70 ± 29, 35 ± 10, and 26 ± 5%, respectively. The membrane content of α1 was not changed by exercise, and the densities of subunits in muscle homogenates were unchanged. The ratio of vesicular to crude muscle homogenate content of the α2-, total α-, and β1-subunits was elevated during exercise by 67 ± 33 ( P < 0.05), 23 ± 6 ( P < 0.05), and 40 ± 14% ( P = 0.06), respectively. It is concluded that translocation of subunits is an important mechanism involved in the short time upregulation of the Na+-K+ pumps in association with human muscle activity.

Human skeletal muscle pyruvate dehydrogenase kinase activity increases after a low-carbohydrate diet

1998 ◽  
Vol 275 (6) ◽  
pp. E980-E986 ◽  
Author(s):  
Sandra J. Peters ◽  
Timothy A. St. Amand ◽  
Richard A. Howlett ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Dehydrogenase ◽  
Human Skeletal Muscle ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Active Form ◽  
Pyruvate Dehydrogenase Kinase ◽  
Acid Oxidation ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate

To characterize human skeletal muscle enzymatic adaptation to a low-carbohydrate, high-fat, and high-protein diet (LCD), subjects consumed a eucaloric diet consisting of 5% of the total energy intake from carbohydrate, 63% from fat, and 33% from protein for 6 days compared with their normal diet (52% carbohydrate, 33% fat, and 14% protein). Biopsies were taken from the vastus lateralis before and after 3 and 6 days on a LCD. Intact mitochondria were extracted from fresh muscle and analyzed for pyruvate dehydrogenase (PDH) kinase, total PDH, and carnitine palmitoyltransferase I activities and mitochondrial ATP production rate (using carbohydrate and fat substrates). β-Hydroxyacyl CoA dehydrogenase, active PDH (PDHa), and citrate synthase activities were also measured on whole muscle homogenates. PDH kinase (PDHK) was calculated as the absolute value of the apparent first-order rate constant of the inactivation of PDH in the presence of 0.3 mM Mg2+-ATP. PDHK increased dramatically from 0.10 ± 0.02 min−1 to 0.35 ± 0.09 min−1 at 3 days and 0.49 ± 0.06 min−1 after 6 days. Resting PDHa activity decreased from 0.63 ± 0.17 to 0.17 ± 0.04 mmol ⋅ min−1 ⋅ kg−1after 6 days on the diet, whereas total PDH activity did not change. Activities for all other enzymes were unaltered by the LCD. In summary, severe deficiency of dietary carbohydrate combined with a twofold increase in dietary fat and protein caused a rapid three- to fivefold increase in PDHK activity in human skeletal muscle. The increased PDHK activity downregulated the amount of PDH in its active form at rest and decreased carbohydrate metabolism. However, an increase in the activities of enzymes involved in fatty acid oxidation did not occur.

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