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K. S. Krabbe,
A. R. Nielsen,
R. Krogh-Madsen,
P. Plomgaard,
P. Rasmussen,
C. Erikstrup,
C. P. Fischer,
B. Lindegaard,
A. M. W. Petersen,
S. Taudorf,
N. H. Secher, H. Pilegaard,
H. Bruunsgaard,
B. K. Pedersen
Diabetologia 04/2012; 50(9):2029-2030. · 6.81 Impact Factor
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ABSTRACT: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice.
Four-month-old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1 h of treadmill exercise, where subcutaneous adipose tissue (AT) was removed either immediately after, 4 h or 10 h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training.
AT leptin mRNA decreased immediately after a single running exercise bout in both genotypes and returned to baseline within 10 h of recovery in IL-6 KO mice, but not WT mice. Leptin mRNA content decreased in WT and increased in IL-6 KO mice with training, but without significant alterations in leptin protein. Acute exercise induced a decrease in the AT TNFα mRNA content in WT, but not in IL-6-KO mice, while training lowered resting levels of TNFα mRNA in both genotypes. In addition, an exercise-induced decline in AT PPARγ mRNA content was absent in IL-6 KO mice and in line training increased PPARγ mRNA only in IL-6 KO mice.
The present findings indicate a role of IL-6 in regulating exercise- and training-induced leptin and PPARγ expression in adipose tissue. In addition, while IL-6 is required for TNF-α mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue.
Acta Physiologica 10/2011; 205(2):224-35. · 3.09 Impact Factor
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ABSTRACT: The aim of this study was to test the hypothesis that interleukin (IL)-6 plays a role in exercise-induced peroxisome proliferator-activated receptor γ co-activator (PGC)-1α and tumor necrosis factor (TNF)-α mRNA responses in skeletal muscle and to examine the potential IL-6-mediated AMP-activated protein kinase (AMPK) regulation in these responses.
Whole body IL-6 knockout (KO) and wildtype (WT) male mice (4 months of age) performed 1 h treadmill exercise. White gastrocnemius (WG) and quadriceps (Quad) muscles were removed immediately (0') or 4 h after exercise and from mice not run acutely.
Acute exercise reduced only in WT muscle glycogen concentration to 55 and 35% (P < 0.05) of resting level in Quad and WG respectively. While AMPK and Acetyl CoA carboxylase (ACC) phosphorylation increased 1.3-fold (P < 0.05) in WG and twofold in Quad immediately after exercise in WT mice, no change was detected in WG in IL-6 KO mice. The PGC-1α mRNA content was in resting WG 1.8-fold higher (P < 0.05) in WT mice than in IL-6 KO mice. Exercise induced a delayed PGC-1α mRNA increase in Quad in IL-6 KO mice (12-fold at 4 h) relative to WT mice (fivefold at 0'). The TNF-α mRNA content was in resting Quad twofold higher (P < 0.05) in IL-6 KO than in WT, and WG TNF-α mRNA increased twofold (P < 0.05) immediately after exercise only in IL-6 KO.
In conclusion, IL-6 affects exercise-induced glycogen use, AMPK signalling and TNF-α mRNA responses in mouse skeletal muscle.
Acta Physiologica 02/2011; 202(2):165-73. · 3.09 Impact Factor
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ABSTRACT: Exercise-induced adaptations in skeletal muscle oxidative enzymes are suggested to result from the cumulative effects of transient changes in gene expression after each single exercise session. However, for several oxidative enzymes, no changes in mRNA expression are detected up to 8 h after exercise. To test the hypothesis that mRNA expression of many oxidative enzymes is up-regulated late in recovery (10-24 h) after exercise, male subjects (n=8) performed a 90-min cycling exercise (70% VO(2-max)), with muscle biopsies obtained before exercise (pre), and after 10, 18 and 24 h of recovery. The mRNA expression of carnitine-palmitoyltransferase (CPT)I, CD36, 3-hydroxyacyl-CoA-dehydrogenase (HAD), cytochrome (Cyt)c, aminolevulinate-delta-synthase (ALAS)1 and GLUT4 was 100-200% higher at 10-24 h of recovery from exercise than in a control trial. Exercise induced a 100-300% increase in peroxisome proliferator-activated receptor gamma co-activator (PGC)-1alpha, citrate synthase (CS), CPTI, CD36, HAD and ALAS1 mRNA contents at 10-24 h of recovery relative to before exercise. No protein changes were detected in Cytc, ALAS1 or GLUT4. This shows that mRNA expression of several training-responsive oxidative enzymes is up-regulated in human skeletal muscle at 10-24 h of recovery, supporting that exercise-induced adaptations of these oxidative enzymes can be the result of the cumulative effects of transient changes in mRNA expression.
Scandinavian Journal of Medicine and Science in Sports 09/2009; 20(4):593-9. · 2.87 Impact Factor
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J T Treebak,
C Frøsig,
C Pehmøller,
S Chen,
S J Maarbjerg,
N Brandt,
C MacKintosh,
J R Zierath,
D G Hardie,
B Kiens,
E A Richter, H Pilegaard,
J F P Wojtaszewski
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ABSTRACT: TBC1 domain family, member 4 (TBC1D4; also known as AS160) is a cellular signalling intermediate to glucose transport regulated by insulin-dependent and -independent mechanisms. Skeletal muscle insulin sensitivity is increased after acute exercise by an unknown mechanism that does not involve modulation at proximal insulin signalling intermediates. We hypothesised that signalling through TBC1D4 is involved in this effect of exercise as it is a common signalling element for insulin and exercise.
Insulin-regulated glucose metabolism was evaluated in 12 healthy moderately trained young men 4 h after one-legged exercise at basal and during a euglycaemic-hyperinsulinaemic clamp. Vastus lateralis biopsies were taken before and immediately after the clamp.
Insulin stimulation increased glucose uptake in both legs, with greater effects (approximately 80%, p < 0.01) in the previously exercised leg. TBC1D4 phosphorylation, assessed using the phospho-AKT (protein kinase B)substrate antibody and phospho- and site-specific antibodies targeting six phosphorylation sites on TBC1D4, increased at similar degrees to insulin stimulation in the previously exercised and rested legs (p < 0.01). However, TBC1D4 phosphorylation on Ser-318, Ser-341, Ser-588 and Ser-751 was higher in the previously exercised leg, both in the absence and in the presence of insulin (p < 0.01; Ser-588, p = 0.09; observed power = 0.39). 14-3-3 binding capacity for TBC1D4 increased equally (p < 0.01) in both legs during insulin stimulation.
We provide evidence for site-specific phosphorylation of TBC1D4 in human skeletal muscle in response to physiological hyperinsulinaemia. The data support the idea that TBC1D4 is a nexus for insulin- and exercise-responsive signals that may mediate increased insulin action after exercise.
Diabetologia 02/2009; 52(5):891-900. · 6.81 Impact Factor
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ABSTRACT: The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-alpha, IL-6 and IL-10 gene promoter regions are risk factors for cognitive decline in healthy octogenarians, and to isolate the strongest inflammatory biomarkers of cognitive function in the peripheral blood. The Wechsler Adult Intelligence Scale was administered to 112 individuals at ages 80 and 85. An IL-18 haplotype was an independent risk factor of poor Performance IQ. The TNF-308GA genotype was related to individual declines in Verbal IQ, and the IL-10-592 CC genotype was related to better Verbal IQ at the age of 80. Circulating levels of TNF-alpha, sTNFRs, and IL-6 were negatively correlated with IQ at age 85 and less strongly to IQ at age 80 with activation of the TNF system as the strongest biomarker. In conclusion, SNPs related to high proinflammatory or low anti-inflammatory activity are independent risk factors of reduced cognitive function in octogenarians. Only the IL-18 haplotype was associated with inflammation in the peripheral blood and only with regard to circulating TNF-alpha.
Neurobiology of aging 11/2007; 30(5):769-81. · 5.94 Impact Factor
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ABSTRACT: Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes.
Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 +/- 11 years; cycling Vo(2peak): males 57.4 +/- 5.9, females 48.1 +/- 4.0 mL kg(-1) min(-1)). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions.
After the race fat mass was decreased by 1.6 +/- 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 +/- 0.06 and 0.93 +/- 0.03 before, to 0.71 +/- 0.01 and 0.85 +/- 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 +/- 74 to 1407 +/- 118 micromol L(-1); P < 0.01). Muscle glycogen content fell 50% (from 554 +/- 28 to 270 +/- 25 nmol kg(-1) d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 +/- 5 to 22 +/- 3 mmol kg(-1) d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor gamma co-activator-1beta mRNA tended to be lower (P = 0.06).
Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes.
Acta Physiologica 10/2007; 191(1):77-86. · 3.09 Impact Factor
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K S Krabbe,
A R Nielsen,
R Krogh-Madsen,
P Plomgaard,
P Rasmussen,
C Erikstrup,
C P Fischer,
B Lindegaard,
A M W Petersen,
S Taudorf,
N H Secher, H Pilegaard,
H Bruunsgaard,
B K Pedersen
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ABSTRACT: Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore explored whether BDNF plays a role in human glucose metabolism.
We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic and a hyperinsulinaemic-euglycaemic clamp.
Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited, indicating that high levels of glucose, but not insulin, inhibit the output of BDNF from the human brain.
Low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a pathogenetic factor involved not only in dementia and depression, but also in type 2 diabetes, potentially explaining the clustering of these conditions in epidemiological studies.
Diabetologia 03/2007; 50(2):431-8. · 6.81 Impact Factor
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ABSTRACT: We compared metabolic gene expression in adipose tissue and skeletal muscle from patients with type 2 diabetes and from well-matched healthy control subjects. We hypothesised that gene expression would be discordantly regulated when comparing the two groups. Our secondary aim was to determine the effect of Interleukin-6 (IL6) infusion on circulating adipokines and on gene expression in human adipose tissue. To do this we used real-time RT-PCR.
Both diabetic and control subjects underwent basal skeletal muscle and subcutaneous adipose tissue biopsies. A subset of these individuals underwent a 3-h infusion of recombinant human IL6 and had adipose tissue samples taken before and after infusion.
The mRNA gene expression of suppressor of cytokine signalling (SOCS) 3, peroxisome proliferative activated receptor (PPAR) alpha/delta, PPAR gamma, coactivator 1, alpha (PPARGC1A), carnitine palmitoyltransferase 1B and solute carrier family 2 (facilitated glucose transporter), member 4 (formerly known as glucose transporter 4/GLUT4), was higher in adipose tissue, but lower in skeletal muscle of diabetic patients than in that of control subjects. In addition, uncoupling protein 1 (UCP1) gene was detected in the adipose tissue of some of the diabetic patients, but not in the control subjects. The following genes were increased by infusion of recombinant human IL6 in both groups: SOCS1/3, resistin, adiponectin, AMP-activated protein kinase-alpha-1 and PPARA. Plasma tumour necrosis factor alpha, adiponectin and resistin were all unaffected by IL6 infusion, but plasma resistin was lower in the diabetic subjects than in control subjects.
The observation that PPARGC1A and the PPARs were upregulated in the adipose tissue of type 2 diabetic patients, along with the finding that adipose tissue from some patients with type 2 diabetes can express UCP1 mRNA, suggests that in these patients white adipose tissue may move towards a brown adipose tissue phenotype.
Diabetologia 06/2006; 49(5):1000-7. · 6.81 Impact Factor
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ABSTRACT: Angiogenesis, the growth of new blood vessels from existing ones, occurs in the skeletal muscle as an adaptive response to exercise that satisfies the increased requirement of this tissue for oxygen delivery and metabolic processes. Of the factors that have been identified to regulate this process, the endothelial cell mitogen vascular endothelial growth factor (VEGF) has been proposed to play a key role. The aim of this study was to measure the skeletal muscle VEGF mRNA content and arteriovenous protein balance across the working leg in response to a single bout of prolonged, submaximal exercise. Seven physically active males completed 3 h of two-legged kicking ergometry. Muscle biopsies were collected from the vastus lateralis muscle from both working legs, and blood samples were collected from one femoral artery and femoral vein before, during, and in recovery from exercise. We show that the exercise stimulus elicited a decrease in VEGF protein arteriovenous balance across the exercising leg (P = 0.007), and a ninefold elevation in skeletal muscle VEGF mRNA expression (P < 0.001). The changes in VEGF protein balance and mRNA content were most pronounced 1 h after the cessation of exercise. In conclusion, these findings demonstrate that submaximal exercise, suitable for humans with low CV fitness, induces a decrease in VEGF arteriovenous balance that is likely to be of clinical significance in promoting angiogenic effects.
AJP Heart and Circulatory Physiology 10/2003; 285(4):H1759-63. · 3.71 Impact Factor
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ABSTRACT: In humans, the plasma interleukin 6 (IL-6) concentration increases dramatically during low-intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL-6 production. To determine whether energy availability influences the regulation of IL-6 expression during prolonged exercise, six male subjects completed two trials consisting of 180 min of two-legged dynamic knee extensor with either normal or low (~60% of control) pre-exercise muscle glycogen levels. Increases in plasma IL-6 during exercise were significantly higher (P<0.05) in the low-glycogen (16-fold) trial verses the control (10-fold) trial. Transcriptional activation of the IL-6 gene in skeletal muscle was also higher in the low-glycogen trial; it increased by about 40-fold after 90 min of exercise and about 60-fold after 180 min of exercise. Muscle IL-6 mRNA followed a similar but delayed pattern, increasing by more than 100-fold in the low-glycogen trial and by about 30-fold in the control trial. These data demonstrate that exercise activates transcription of the IL-6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. These findings also support the hypothesis that IL-6 may be produced by contracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.
The FASEB Journal 12/2001; 15(14):2748-50. · 5.71 Impact Factor
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ABSTRACT: Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60-90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to beta-actin) increased by three- to sevenfold in response to exercise, peaking after 1-2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise (n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.
AJP Endocrinology and Metabolism 11/2000; 279(4):E806-14. · 4.75 Impact Factor
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ABSTRACT: Interstitial K(+) concentrations were measured during one-legged knee-extensor exercise by use of microdialysis with probes inserted in the vastus lateralis muscle of the subjects. K(+) in the dialysate was measured either by flame photometry or a K(+)-sensitive electrode placed in the perfusion outlet. The correction for fractional K(+) recovery was based on the assumption of identical fractional thallium loss. The interstitial K(+) was 4. 19 +/- 0.09 mM at rest and increased to 6.17 +/- 0.19, 7.48 +/- 1.18, and 9.04 +/- 0.74 mM at 10, 30, and 50 W exercise, respectively. The individual probes demonstrated large variations in interstitial K(+), and values >10 mM were obtained. The observed interstitial K(+) was markedly higher than previously found for venous K(+) concentrations at similar work intensities. The present data support a potential role for interstitial K(+) in regulation of blood flow and development of fatigue.
AJP Regulatory Integrative and Comparative Physiology 02/2000; 278(2):R400-6. · 3.34 Impact Factor
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ABSTRACT: The profiles of the lactate/H+ transporter isoforms [monocarboxylate transporter isoforms (MCT)] MCT1 and MCT4 (formerly MCT3 of Price, N. T., V. N. Jackson, and A. P. Halestrap. Biochem. J. 329: 321-328, 1998) were studied in the soleus, triceps brachii, and vastus lateralis muscles of six male subjects. The fiber-type compositions of the muscles were evaluated from the occurrence of the myosin heavy chain isoforms, and the fibers were classified as type I, IIA, or IIX. The total content of MCT1 and MCT4 was determined in muscle homogenates by Western blotting, and MCT1 and MCT4 were visualized on cross-sectional muscle sections by immunofluorescence microscopy. The Western blotting revealed a positive, linear relationship between the MCT1 content and the occurrence of type I fibers in the muscle, but no significant relation was found between MCT4 content and fiber type. Moreover, the interindividual variation in MCT4 content was much larger than the interindividual variation in MCT1 content in homogenate samples. The immunofluorescence microscopy showed that within a given muscle section, the MCT4 isoform was clearly more abundant in type II fibers than in type I fibers, whereas only minor differences existed in the occurrence of the MCT1 isoform between type I and II fibers. Together the present results indicate that the content of MCT1 in a muscle varies between different muscles, whereas fiber-type differences in MCT1 content are minor within a given muscle section. In contrast, the content of MCT4 is clearly fiber-type specific but apparently quite similar in various muscles.
The American journal of physiology 06/1999; 276(5 Pt 1):E843-8.
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ABSTRACT: The present study examined the effect of high-intensity exercise training on muscle sarcolemmal lactate/H+ transport and the monocarboxylate transporters (MCT1 and MCT4) as well as lactate and H+ release during intense exercise in humans. One-legged knee-extensor exercise training was performed for 8 wk, and biopsies were obtained from untrained and trained vastus lateralis muscle. The rate of lactate/H+ transport determined in sarcolemmal giant vesicles was 12% higher (P < 0.05) in the trained than in untrained muscle (n = 7). The content of MCT1 and MCT4 protein was also higher (76 and 32%, respectively; n = 4) in trained muscle. Release of lactate and H+ from the quadriceps muscle at the end of intense exhaustive knee-extensor exercise was similar in the trained and untrained leg, although the estimated muscle intracellular-to-interstitial gradients of lactate and H+ were lower (P < 0.05) in the trained than in the untrained muscle. The present data show that intense exercise training can increase lactate/H+ transport capacity in human skeletal muscle as well as improve the ability of the muscle to release lactate and H+ during contractions.
The American journal of physiology 02/1999; 276(2 Pt 1):E255-61.
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ABSTRACT: The present study compared the microdialysis ethanol outflow-inflow technique for estimating blood flow (BF) in skeletal muscle of humans with measurements by Doppler ultrasound of femoral artery inflow to the limb (BFFA). The microdialysis probes were inserted in the vastus lateralis muscle and perfused with a Ringer acetate solution containing ethanol, [2-3H]adenosine (Ado), and D-[14C(U)]glucose. BFFA at rest increased from 0.16 +/- 0.02 to 1.80 +/- 0.26 and 4.86 +/- 0.53 l/min with femoral artery infusion of Ado (AdoFA,i) at 125 and 1,000 microg . min-1 . l-1 thigh volume (low dose and high dose, respectively; P < 0.05) and to 3.79 +/- 0.37 and 6.13 +/- 0.65 l/min during one-legged, dynamic, thigh muscle exercise without and with high AdoFA,i, respectively (P < 0.05). The ethanol outflow-to-inflow ratio (38.3 +/- 2.3%) and the probe recoveries (PR) for [2-3H]Ado (35.4 +/- 1.6%) and for D-[14C(U)]glucose (15.9 +/- 1.1%) did not change with AdoFA,i at rest (P = not significant). During exercise without and with AdoFA,i, the ethanol outflow-to-inflow ratio decreased (P < 0.05) to a similar level of 17.5 +/- 3.4 and 20.6 +/- 3.2%, respectively (P = not significant), respectively, while the PR increased (P < 0.05) to a similar level (P = not significant) of 55.8 +/- 2.8 and 61.2 +/- 2. 5% for [2-3H]Ado and to 42.8 +/- 3.9 and 45.2 +/- 5.1% for D-[14C(U)]glucose. Whereas the ethanol outflow-to-inflow ratio and PR correlated inversely and positively, respectively, to the changes in BF during muscular contractions, neither of the ratio nor PR correlated to the AdoFA,i-induced BF increase. Thus the ethanol outflow-to-inflow ratio does not represent skeletal muscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.
Journal of Applied Physiology 08/1998; 85(2):751-7. · 3.75 Impact Factor
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ABSTRACT: The newly cloned proton-linked monocarboxylate transporter MCT3 was shown by Western blotting and immunofluorescence confocal microscopy to be expressed in all muscle fibers. In contrast, MCT1 is expressed most abundantly in oxidative fibers but is almost totally absent in fast-twitch glycolytic fibers. Thus MCT3 appears to be the major MCT isoform responsible for efflux of glycolytically derived lactic acid from white skeletal muscle. MCT3 is also expressed in several other tissues requiring rapid lactic acid efflux. The expression of both MCT3 and MCT1 was decreased by 40-60% 3 weeks after denervation of rat hind limb muscles, whereas chronic stimulation of the muscles for 7 days increased expression of MCT1 2-3-fold but had no effect on MCT3 expression. The kinetics and substrate and inhibitor specificities of monocarboxylate transport into cell lines expressing only MCT3 or MCT1 have been determined. Differences in the properties of MCT1 and MCT3 are relatively modest, suggesting that the significance of the two isoforms may be related to their regulation rather than their intrinsic properties.
Journal of Biological Chemistry 07/1998; 273(26):15920-6. · 4.77 Impact Factor
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ABSTRACT: In order to evaluate the effect of prolonged muscle inactivity on sarcolemmal lactate/H+ transport in humans, the lactate/H+ transport capacity was determined in the thigh muscle of spinal-cord-injured (SCI) individuals. The lactate transport rate was measured in sarcolemmal giant vesicles produced by collagenase treatment of muscle biopsies obtained from the vastus lateralis muscle. Six SCI subjects with total loss of motor and sensory functions of their lower limbs participated in the study. The duration of the injury ranged from 2 to 15 years. The total lactate transport rate in the muscle of SCI patients was 46.5 +/- 2.6 pmol.cm-2.s-1 (mean +/- SEM), which corresponds to a 17% lower (P < 0.05) transport rate than that found in healthy, untrained subjects. The estimated carrier-mediated lactate/H+ transport capacity was approximately 26% lower in the SCI patients than in healthy, untrained subjects. The observed muscle lactate/H+ transport capacity of SCI individuals is in accordance with a positive correlation between the capacity of the lactate/H+ transporters and the percentage occurrence of slow-twitch fibres in a muscle, although there seems to be a wide range of transport capacities within each fibre type. The present results show that the sarcolemmal lactate/H+ transport capacity is lower in SCI individuals than in normally physically active subjects, which indicates that prolonged muscle inactivity reduces the lactate/H+ transport capacity of human muscle.
Scandinavian Journal of Medicine and Science in Sports 04/1998; 8(2):98-101. · 2.87 Impact Factor
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ABSTRACT: The effect of prior eccentric contractions on skeletal muscle lactate/H+ transport was investigated in rats. Lactate transport was measured in sarcolemmal giant vesicles obtained from soleus and red (RG) and white gastrocnemii (WG) muscles 2 days after intense eccentric contractions (ECC) and from the corresponding contralateral control (CON) muscles. The physiochemical buffer capacity was determined in the three muscle types from both ECC and CON legs. Furthermore, the effect of prior eccentric contractions on release and muscle content of lactate and H+ during and after supramaximal stimulation was examined using the perfused rat hindlimb preparation. The lactate transport rate was lower (P < 0.05) in vesicles obtained from ECC-WG (29%) and ECC-RG (13%) than in vesicles from the CON muscles. The physiochemical buffer capacity was reduced (P < 0.05) in ECC-WG (13%) and ECC-RG (9%) compared with the corresponding CON muscles. There were only marginal effects on the soleus muscle. Muscle lactate concentrations and release of lactate during recovery from intense isometric contractions were lower (P < 0.05) in ECC than in CON hindlimbs, indicating decreased anaerobic glycogenolysis. In conclusion, the sarcolemmal lactate/H+ transport capacity and the physiochemical buffer capacity were reduced in prior eccentrically stimulated WG and RG in rats, suggesting that muscle pH regulation may be impaired after unaccustomed eccentric exercise. In addition, the data indicate that the glycogenolytic potential is decreased in muscles exposed to prior eccentric contractions.
The American journal of physiology 03/1998; 274(3 Pt 1):E554-9.
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ABSTRACT: The influence of blood flow on muscle lactate and H+ release as well as muscle glyconeogenesis was studied in the perfused rat hindlimb. After 2 min of supramaximal stimulation the perfusate flow rate was 7 (F7), 12 (F12), or 18 (F18) ml/min for 30 min. Perfusate samples were drawn frequently and muscle samples were obtained before stimulation, immediately after stimulation, and at 3, 10, and 30 min of recovery from soleus, white gastrocnemius (WG) and red gastrocnemius. During the first 5 min of recovery lactate release was 35-39% lower (P < 0.05) in F7 than in F12 and F18 but with no differences in total release during recovery. In F7 the concentration of lactate was higher (P < 0.05) in soleus after 10 min (18-20%) and in WG after 30 min (63-67%) than in F12 and F18. During the first 2 min of recovery H+ release was 23-34% lower (P < 0.05) in F7 than in F12 and F18. The difference between H+ and lactate release was larger (P < 0.05) in F7 than in F12 and F18 from 3 to 10 min and from 5 to 10 min of recovery, respectively. Muscle glycogen concentrations after 30 min of recovery were independent of flow in each of the muscles. The present data suggest that 1) in the range of blood flow rates from 0.61 to 0.92 ml.min-1.g-1, lactate and H+ release are independent of the flow rate, whereas at a lower flow rate (0.36 ml.min-1.g-1) release of these substances is decreased; 2) low blood flow influences lactate efflux more than H+ release; and 3) muscle glyconeogenesis from lactate is of minor importance.
The American journal of physiology 01/1996; 269(6 Pt 1):E1044-51.
