Rapid upregulation of GLUT-4 and MCT-4 expression during 16 h of heavy intermittent cycle exercise

2008 ◽  
Vol 294 (2) ◽  
pp. R594-R600 ◽  
Author(s):  
H. J. Green ◽  
T. A. Duhamel ◽  
G. P. Holloway ◽  
J. W. Moule ◽  
D. W. Ranney ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Aerobic Power ◽  
Vastus Lateralis ◽  
Fold Increase ◽  
Monocarboxylate Transporter ◽  
Glycolytic Flux ◽  
Exercise Protocol ◽  
Cycle Exercise ◽  
Muscle Lactate ◽  
Glut 4

In this study, we have investigated the hypothesis that an exercise protocol designed to repeatedly induce a large dependence on carbohydrate and large increases in glycolytic flux rate would result in rapid increases in the principal glucose and lactate transporters in working muscle, glucose transporter (GLUT)-4 and monocarboxylate transporter (MCT)4, respectively, and in activity of hexokinase (Hex), the enzyme used to phosphorylate glucose. Transporter abundance and Hex activity were assessed in homogenates by Western blotting and quantitative chemiluminescence and fluorometric techniques, respectively, in samples of tissue obtained from the vastus lateralis in 12 untrained volunteers [peak aerobic power (V̇o2peak) = 44.3 ± 2.3 ml·kg−1·min−1] before cycle exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). The 16 repetitions of the exercise were performed for 6 min at ∼90% V̇o2peak, once per hour. Compared with R1, GLUT-4 increased ( P < 0.05) by 28% at R2 and remained elevated ( P < 0.05) at R9 and R16. For MCT-4, increases ( P < 0.05) of 24% were first observed at R9 and persisted at R16. No changes were observed in GLUT-1 and MCT-1 or in Hex activity. The ∼17- to 24-fold increase ( P < 0.05) in muscle lactate observed at R1 and R2 was reduced ( P < 0.05) to an 11-fold increase at R9 and R16. It is concluded that an exercise protocol designed to strain muscle carbohydrate reserves and to result in large increases in lactic acid results in a rapid upregulation of both GLUT-4 and MCT-4.

Muscle Na+-K+-ATPase response during 16 h of heavy intermittent cycle exercise

2007 ◽  
Vol 293 (2) ◽  
pp. E523-E530 ◽  
Author(s):  
H. J. Green ◽  
T. A. Duhamel ◽  
G. P. Holloway ◽  
J. W. Moule ◽  
J. Ouyang ◽  
...  
Keyword(s):  
Aerobic Power ◽  
Intermittent Exercise ◽  
Binding Capacity ◽  
Vastus Lateralis ◽  
Intrinsic Activity ◽  
Cycle Exercise ◽  
Maximum Binding Capacity ◽  
Phosphatase Assay ◽  
Quantitative Immunoblotting

This study investigated the effects of a 16-h protocol of heavy intermittent exercise on the intrinsic activity and protein and isoform content of skeletal muscle Na+-K+-ATPase. The protocol consisted of 6 min of exercise performed once per hour at ∼91% peak aerobic power (V̇o2 peak) with tissue sampling from vastus lateralis before (B) and immediately after repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). Eleven untrained volunteers with a V̇o2 peak of 44.3 ± 2.3 ml·kg−1·min−1 participated in the study. Maximal Na+-K+-ATPase activity ( Vmax, in nmol·mg protein−1·h−1) as measured by the 3- O-methylfluorescein K+-stimulated phosphatase assay was reduced ( P < 0.05) by ∼15% with exercise regardless of the number of repetitions performed. In addition, Vmax at R9 and R16 was lower ( P < 0.05) than at R1 and R2. Vanadate-facilitated [3H]ouabain determination of Na+-K+-ATPase content (maximum binding capacity, pmol/g wet wt), although unaltered by exercise, increased ( P < 0.05) 8.3% by R9 with no further increase observed at R16. Assessment of relative changes in isoform abundance measured at B as determined by quantitative immunoblotting showed a 26% increase ( P < 0.05) in the α2-isoform by R2 and a 29% increase in α3 by R9. At R16, β3 was lower ( P < 0.05) than at R2 and R9. No changes were observed in α1, β1, or β2. It is concluded that repeated sessions of heavy exercise, although resulting in increases in the α2- and α3-isoforms and decreases in β3-isoform, also result in depression in maximal catalytic activity.

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.

Metabolic changes in skeletal muscle and blood of greyhounds during 800-m track sprint

1988 ◽  
Vol 255 (3) ◽  
pp. R513-R519 ◽  
Author(s):  
G. P. Dobson ◽  
W. S. Parkhouse ◽  
J. M. Weber ◽  
E. Stuttard ◽  
J. Harman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Fold Increase ◽  
Biceps Femoris ◽  
Muscle Lactate ◽  
Muscle Ph ◽  
The Mean ◽  
Metabolic Properties ◽  
Fast Twitch ◽  
Anaerobic Conversion

The aim of this study was to examine some metabolic properties and changes that occur in skeletal muscle and blood of greyhounds after an 800-m sprint. Three prime moving fast-twitch muscles were selected: biceps femoris (BF), gastrocnemius (G), and vastus lateralis (VL). The amount of glycogen utilized during the event was 42.57, 43.86, and 42.73 mumol glucosyl units/g wet wt, respectively. Expressed as a function of race time (48.3 +/- 0.7 s, n = 3), the mean rate of glycogen breakdown was 53.48 +/- 0.5 mumol.g wet wt-1.min-1 during the sprint. This is equivalent to an ATP turnover of 160 mumol.g wet wt-1.min-1, assuming 100% anaerobic conversion to lactate. This represents a conservative estimate, since greyhound muscle is heterogeneous and comprised of a large percentage of fast-twitch oxidative fibers (Armstrong et al., Am. J. Anat. 163: 87-98, 1982). The large decrease in muscle glycogen was accompanied by a 6- to 7-fold increase in muscle lactate from 3.48 +/- 0.13 to 25.42 +/- 3.54 (BF), 2.54 +/- 1.05 to 18.96 +/- 2.60 (G), and 4.57 +/- 0.44 to 30.09 +/- 1.94 mumol.g wet wt (VL), and a fall in muscle pH from 6.88 +/- 0.03 to 6.40 +/- 0.02 (BF), 6.92 +/- 0.02 to 6.56 +/- 0.02 (G), and 6.93 +/- 0.02 to 6.47 +/- 0.01 (VL). Cytosolic phosphorylation potential in BF decreased 10-fold from 11,360 +/- 680 to 1,184 +/- 347, and redox potential decreased 5-fold, indicating a marked reduction in the cytosol at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease

2008 ◽  
Vol 105 (3) ◽  
pp. 879-886 ◽  
Author(s):  
H. J. Green ◽  
M. E. Burnett ◽  
C. L. D'Arsigny ◽  
D. E. O'Donnell ◽  
J. Ouyang ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Glucose Transporter ◽  
Adenine Nucleotide ◽  
Vastus Lateralis ◽  
Glycogen Storage ◽  
Forced Expiratory Volume ◽  
Glycolytic Flux ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV1) = 42 ± 6.0% (mean ± SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV1 = 114 ± 3.4%). Compared with controls, lower ( P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 ± 0.65 vs. 17.8 ± 0.69) and phosphocreatine (81.3 ± 2.3 vs. 69.1 ± 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 ± 20 vs. 269 ± 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.

scholarly journals Translocation of the brain-type glucose transporter largely accounts for insulin stimulation of glucose transport in BC3H-1 myocytes

1990 ◽  
Vol 269 (3) ◽  
pp. 597-601 ◽  
Author(s):  
D M Calderhead ◽  
K Kitagawa ◽  
G E Lienhard ◽  
G W Gould
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Fold Increase ◽  
The Other ◽  
Insulin Stimulation ◽  
Glut 1 ◽  
Glut 4 ◽  
Rat Soleus Muscle ◽  
The Brain ◽  
Stimulation Of

Insulin-stimulated glucose transport was examined in BC3H-1 myocytes. Insulin treatment lead to a 2.7 +/- 0.3-fold increase in the rate of deoxyglucose transport and, under the same conditions, a 2.1 +/- 0.1-fold increase in the amount of the brain-type glucose transporter (GLUT 1) at the cell surface. It has been shown that some insulin-responsive tissues express a second, immunologically distinct, transporter, namely GLUT 4. We report here that BC3H-1 myocytes and C2 and G8 myotubes express only GLUT 1; in contrast, rat soleus muscle and heart express 3-4 times higher levels of GLUT 4 than GLUT 1. Thus translocation of GLUT 1 can account for most, if not all, of the insulin stimulation of glucose transport in BC3H-1 myocytes. On the other, hand, neither BC3H-1 myocytes nor the other muscle-cell lines are adequate as models for the study of insulin regulation of glucose transport in muscle tissue.

Short-term training increases human muscle MCT1 and femoral venous lactate in relation to muscle lactate

1998 ◽  
Vol 274 (1) ◽  
pp. E102-E107 ◽  
Author(s):  
A. Bonen ◽  
K. J. A. McCullagh ◽  
C. T. Putman ◽  
E. Hultman ◽  
N. L. Jones ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vastus Lateralis ◽  
Venous Blood ◽  
Maximal Oxygen Consumption ◽  
Bicycle Ergometer ◽  
Monocarboxylate Transporter ◽  
Short Term ◽  
Bicycle Ergometry ◽  
Muscle Lactate ◽  
Monocarboxylate Transporter 1

We examined the effects of increasing a known lactate transporter protein, monocarboxylate transporter 1 (MCT1), on lactate extrusion from human skeletal muscle during exercise. Before and after short-term bicycle ergometry training [2 h/day, 7 days at 65% maximal oxygen consumption (V˙o 2 max)], subjects ( n = 7) completed a continuous bicycle ergometer ride at 30%V˙o 2 max (15 min), 60%V˙o 2 max (15 min), and 75% V˙o 2 max (15 min). Muscle biopsy samples (vastus lateralis) and arterial and femoral venous blood samples were obtained before exercise and at the end of each workload. After 7 days of training the MCT1 content in muscle was increased (+18%; P < 0.05). The concentrations of both muscle lactate and femoral venous lactate were reduced during exercise ( P < 0.05) that was performed after training. High correlations were observed between muscle lactate and venous lactate before training ( r = 0.92, P < 0.05) and after training ( r = 0.85, P < 0.05), but the slopes of the regression lines between these variables differed markedly. Before training, the slope was 0.12 ± 0.01 mM lactate ⋅ mmol lactate−1 ⋅ kg muscle dry wt−1, and this was increased by 33% after training to 0.18 ± 0.02 mM lactate ⋅ mmol lactate−1 ⋅ kg muscle dry wt−1. This indicated that after training the femoral venous lactate concentrations were increased for a given amount of muscle lactate. These results suggest that lactate extrusion from exercising muscles is increased after training, and this may be associated with the increase in skeletal muscle MCT1.

Decreased expression of glucose transporter in muscle from insulin-resistant patients

1991 ◽  
Vol 260 (3) ◽  
pp. E459-E463 ◽  
Author(s):  
G. L. Dohm ◽  
C. W. Elton ◽  
J. E. Friedman ◽  
P. F. Pilch ◽  
W. J. Pories ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Obese Patients ◽  
Insulin Resistant ◽  
Glut 4 ◽  
Obesity And Diabetes

We have observed that in vitro incubated human muscle fiber strips from obese patients with or without non-insulin-dependent diabetes mellitus (NIDDM) have reduced insulin-stimulated glucose transport rates compared with nonobese control patients. To investigate if the decrease in glucose transport is associated with a depletion of glucose transport protein, we performed Western blot analysis of muscle samples from nonobese control, obese nondiabetic, and obese NIDDM patients to measure the levels of the muscle-adipose tissue glucose transporter (GLUT-4) protein. Glucose transporter protein was depressed by 23% in the obese nondiabetic and 18% in the obese NIDDM group. The results were essentially the same in the rectus abdominus and vastus lateralis muscles. These data suggest that the decreased glucose transport rate observed in muscle of these obese patients with or without NIDDM may be due, at least in part, to a decreased expression of the "insulin-sensitive" (GLUT-4) glucose transporter. This alteration may play a role in the insulin resistance seen in obesity and diabetes.

Insulin induces translocation of GLUT-4 glucose transporters in human skeletal muscle

1995 ◽  
Vol 268 (4) ◽  
pp. E613-E622 ◽  
Author(s):  
A. Guma ◽  
J. R. Zierath ◽  
H. Wallberg-Henriksson ◽  
A. Klip
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Vastus Lateralis ◽  
Glucose Transporters ◽  
Membrane Markers ◽  
Glut 4 ◽  
Muscle Biopsies

Understanding the molecular mechanisms involved in the regulation of glucose transport into human muscle is necessary to unravel possible defects in glucose uptake associated with insulin resistance in humans. Here we report a strategy to subfractionate human skeletal muscle biopsies (0.5 g) removed from vastus lateralis during a euglycemic insulinemic clamp procedure. A sucrose gradient separated total membranes into five fractions. Fraction 25 (25% sucrose) contained the plasma membrane markers alpha 1- and alpha 2-subunits of the Na(+)-K(+)-adenosinetriphosphatase and the GLUT-5 hexose transporter, recently immunolocalized to the cell surface of human skeletal muscle. The dihydropyridine receptor, a transverse tubule marker, was present exclusively in this fraction. The GLUT-4 glucose transporter was more concentrated in fraction 27.5 (27.5% sucrose) and largely diminished in plasma membrane markers. Open skeletal muscle biopsies were removed before and 30 min after clamping insulin to 550 pM. This increased GLUT-4 protein by 1.61-fold in fraction 25 and lowered it by 50% in fraction 27.5. Thus physiological concentrations of insulin induce translocation of glucose transporters from an internal membrane pool to surface membranes in human skeletal muscle.

scholarly journals Phorbol ester only partially mimics the effects of insulin on glucose transport and glucose-transporter distribution in 3T3-L1 adipocytes

1991 ◽  
Vol 275 (1) ◽  
pp. 145-150 ◽  
Author(s):  
E M Gibbs ◽  
D M Calderhead ◽  
G D Holman ◽  
G W Gould
Keyword(s):  
Plasma Membrane ◽  
Phorbol Ester ◽  
Glucose Transporter ◽  
Fold Increase ◽  
Hexose Transport ◽  
Glut 1 ◽  
Glut 4 ◽  
Glucose Analogue ◽  
Stimulation Of

We examined the effects of the phorbol ester phorbol 12-myristate 13-acetate (PMA) on the rate of hexose transport into 3T3-L1 adipocytes. Exposure of adipocytes to PMA (1 microM) for 60 min results in a 1.7-2.5-fold increase in the rate of hexose transport. This effect was mediated by translocation of two isoforms of glucose transporters to the plasma membrane, as determined by labelling in situ, photoaffinity labelling with a membrane-impermeant glucose analogue, and by immunoblotting of subcellular fractions. The PMA-induced stimulation of both transport and transporter translocation was substantially less than that induced by insulin in this cell line; the PMA-induced increase in plasma-membrane GLUT 1 and GLUT 4 transporter isoforms was only about 40% and 10% respectively of that induced by insulin. We suggest that the stimulation of transport by insulin and PMA occurs via different mechanisms, which is manifested by the ability of insulin to induce a much greater increase in the plasma-membrane content of GLUT 4 compared with the phorbol ester.

Increases in muscle MCT are associated with reductions in muscle lactate after a single exercise session in humans

2002 ◽  
Vol 282 (1) ◽  
pp. E154-E160 ◽  
Author(s):  
H. Green ◽  
A. Halestrap ◽  
C. Mockett ◽  
D. O'Toole ◽  
S. Grant ◽  
...  
Keyword(s):  
Vastus Lateralis ◽  
Training Session ◽  
Exercise Session ◽  
Vastus Lateralis Muscle ◽  
Single Session ◽  
Cycle Exercise ◽  
Muscle Lactate ◽  
Metabolic Adaptations ◽  
Exercise Muscle ◽  
Lactate Levels

To investigate the effects of a single session of prolonged cycle exercise [60% peak O2 uptake (V˙o 2 peak) for 5–6 h] on metabolic adaptations in working vastus lateralis muscle, nine untrained males (peak O2 uptake = 47.2 ± 1.1 ml · kg−1 · min−1, means ± SE) were examined before (Pre) and at 2 (Post-2), 4 (Post-4), and 6 (Post-6) days after the training session. On the basis of 15 min of cycle exercise at 59% V˙o 2 peak, it was found that training reduced ( P < 0.05) exercise muscle lactate (mM) at Post-2 (6.65 ± 0.69), Post-4 (7.74 ± 0.63), and Post-6 (7.78 ± 1.2) compared with Pre (10.9 ± 1.3). No effect of training was observed on exercise ATP, phosphocreatine, and glycogen levels. After the single session of training, plasma volumes were elevated ( P < 0.05) at Post-2 (6.7 ± 1.7%), Post-4 (5.86 ± 1.9), and Post-6 (5.13 ± 2.5). The single exercise session also resulted in elevations ( P< 0.05) in the monocarboxylate transporters MCT1 and MCT4 throughout the 6 days after exercise. Although epinephrine and norepinephrine both increased with exercise, only norepinephrine was reduced ( P < 0.05) with training and only at Post-4. These results indicate that regulation of cellular lactate levels occurs rapidly and independently of other metabolic adaptations. It is proposed that increases in MCT and plasma volume are at least partly involved in the lower muscle lactate content observed after the training session by increasing lactate membrane transport and removal, respectively.

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