Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise

2004 ◽  
Vol 97 (6) ◽  
pp. 2148-2153 ◽  
Author(s):  
Paul J. LeBlanc ◽  
Krista R. Howarth ◽  
Martin J. Gibala ◽  
George J. F. Heigenhauser

This is the first study to examine the effects of endurance training on the activation state of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in human skeletal muscle during exercise. We hypothesized that 7 wk of endurance training (Tr) would result in a posttransformationally regulated decrease in flux through Phos and an attenuated activation of PDH during exercise due to alterations in key allosteric modulators of these important enzymes. Eight healthy men (22 ± 1 yr) cycled to exhaustion at the same absolute workload (206 ± 5 W; ∼80% of initial maximal oxygen uptake) before and after Tr. Muscle biopsies (vastus lateralis) were obtained at rest and after 5 and 15 min of exercise. Fifteen minutes of exercise post-Tr resulted in an attenuated activation of PDH (pre-Tr: 3.75 ± 0.48 vs. post-Tr: 2.65 ± 0.38 mmol·min−1·kg wet wt−1), possibly due in part to lower pyruvate content (pre-Tr: 0.94 ± 0.14 vs. post-Tr: 0.46 ± 0.03 mmol/kg dry wt). The decreased pyruvate availability during exercise post-Tr may be due to a decreased muscle glycogenolytic rate (pre-Tr: 13.22 ± 1.01 vs. post-Tr: 7.36 ± 1.26 mmol·min−1·kg dry wt−1). Decreased glycogenolysis was likely mediated, in part, by posttransformational regulation of Phos, as evidenced by smaller net increases in calculated muscle free ADP (pre-Tr: 111 ± 16 vs. post-Tr: 84 ± 10 μmol/kg dry wt) and Pi (pre-Tr: 57.1 ± 7.9 vs. post-Tr: 28.6 ± 5.6 mmol/kg dry wt). We have demonstrated for the first time that several signals act to coordinately regulate Phos and PDH, and thus carbohydrate metabolism, in human skeletal muscle after 7 wk of endurance training.

2005 ◽  
Vol 288 (6) ◽  
pp. E1265-E1269 ◽  
Author(s):  
Anne Lene Dalkjær Riis ◽  
Jens Otto Lunde Jørgensen ◽  
Niels Møller ◽  
Jørgen Weeke ◽  
Torben Clausen

Skeletal muscle constitutes the major target organ for the thermogenic action of thyroid hormone. We examined the possible relation between energy expenditure (EE), thyroid status, and the contents of Ca2+-ATPase and Na+-K+-ATPasein human skeletal muscle. Eleven hyperthyroid patients with Graves' disease were studied before and after medical treatment with methimazole and compared with eight healthy subjects. Muscle biopsies were taken from the vastus lateralis muscle, and EE was determined by indirect calorimetry. Before treatment, the patients had two- to fivefold elevated total plasma T3 and 41% elevated EE compared with when euthyroidism had been achieved. In hyperthyroidism, the content of Ca2+-ATPase was increased: (mean ± SD) 6,555 ± 604 vs. 5,212 ± 1,580 pmol/g in euthyroidism ( P = 0.04) and 4,523 ± 1,311 pmol/g in healthy controls ( P = 0.0005). The content of Na+-K+-ATPase showed 89% increase in hyperthyroidism: 558 ± 101 vs. 296 ± 34 pmol/g ( P = 0.0001) in euthyroidism and 278 ± 52 pmol/g in healthy controls ( P < 0.0001). In euthyroidism, the contents of both cation pumps did not differ from those of healthy controls. The Ca2+-ATPase content was significantly correlated to plasma T3 and resting EE. This provides the first evidence that, in human skeletal muscle, the capacity for Ca2+ recycling and active Na+-K+ transport are correlated to EE and thyroid status.


1996 ◽  
Vol 270 (2) ◽  
pp. E328-E335 ◽  
Author(s):  
A. Chesley ◽  
G. J. Heigenhauser ◽  
L. L. Spriet

The purpose of this study was to examine the regulation (hormonal, substrate, and allosteric) of muscle glycogen phosphorylase (Phos) activity and glycogenolysis after short-term endurance training. Eight untrained males completed 6 days of cycle exercise (2 h/day) at 65% of maximal O2 uptake (Vo2max). Before and after training subjects cycled for 15 min at 80% of Vo2max, and muscle biopsies and blood samples were obtained at 0 and 30 s, 7.5 and 15 min, and 0, 5, 10, and 15 min of exercise. Vo2max was unchanged with training but citrate synthase (CS) activity increased by 20%. Muscle glycogenolysis was reduced by 42% during the 15-min exercise challenge following training (198.8 +/- 36.9 vs. 115.4 +/- 25.1 mmol/kg dry muscle), and plasma epinephrine was blunted at 15 min of exercise. The Phos a mole fraction was unaffected by training. Muscle phosphocreatine utilization and free Pi and AMP accumulations were reduced with training at 7.5 and 15 min of exercise. It is concluded that posttransformational control of Phos, exerted by reductions in substrate (free Pi) and allosteric modulator (free AMP) contents, is responsible for a blunted muscle glycogenolysis after 6 days of endurance training. The increase in CS activity suggests that the reduction of muscle glycogenolysis was due in part to an enhanced mitochondrial potential.


2000 ◽  
Vol 278 (3) ◽  
pp. E522-E534 ◽  
Author(s):  
Michelle L. Parolin ◽  
Lawrence L. Spriet ◽  
Eric Hultman ◽  
Melanie G. Hollidge-Horvat ◽  
Norman L. Jones ◽  
...  

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O2 (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free Pi, in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDHa) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [Pi]. At the end of exercise, PDHawas greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.


1989 ◽  
Vol 259 (3) ◽  
pp. 901-904 ◽  
Author(s):  
Y Kida ◽  
A Katz ◽  
A D Lee ◽  
D M Mott

Activities of glycogen synthase (GS) and GS phosphatase were determined on human muscle biopsies before and after isometric contraction at 2/3 maximal voluntary force. Total GS activity did not change during contraction (4.92 +/- 0.70 at rest versus 5.00 +/- 0.42 mmol/min per kg dry wt.; mean +/- S.E.M.), whereas both the active form of GS and the ratio of active form to total GS decreased by approximately 35% (P less than 0.01). GS phosphatase was inactivated in all subjects by an average of 39%, from 5.95 +/- 1.30 to 3.63 +/- 0.97 mmol/min per kg dry wt. (P less than 0.01). It is suggested that at least part of the contraction-induced inactivation of GS is due to an inactivation of GS phosphatase.


1995 ◽  
Vol 268 (4) ◽  
pp. E613-E622 ◽  
Author(s):  
A. Guma ◽  
J. R. Zierath ◽  
H. Wallberg-Henriksson ◽  
A. Klip

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.


Author(s):  
Jung-Piao Taso ◽  
Su-Fen Liao ◽  
Duen-Kai Shiau ◽  
Mei-Fang Wu ◽  
Chia-Chen Chang ◽  
...  

We investigated whether post-exercise capsinoids (CSN) supplementation could enhance muscle glycogen resynthesis via GLUT4/Akt expressions in human skeletal muscle. Nine male college students (aged 21.4&plusmn;0.2 years, BMI 21.9&plusmn;1.3 kg/m2, VO2max 47.1&plusmn;1.8 ml/kg/min) participated in this crossover designed study, and completed a 60-min cycling exercise at 70% VO2max. Immediately after exercise, participants consumed high-carbohydrate diet (2 g carb/kg bodyweight) with CSN (12 mg, single dosage) or placebo. Biopsied muscle samples (vastus lateralis) were obtained immediately (0h) and 3h after exercise. Blood and expired gas samples were collected before and after exercise. We found oral CSN supplementation immediately after exercise was unable to enhance glycogen resynthesis in exercised human skeletal muscle. Despite, CSN could alter the energy reliance on fat oxidation during post-exercise recovery, based on gaseous exchange measurement (NEFA and glycerol). We further identified no significant differences in postprandial glucose/insulin area under curve in both trials. Western blot data showed no significant response of p-Akt/Akt ratio with CSN during post-exercise recovery. Inconsistent with glycogen levels, muscle GLUT4 expression was significantly elevated at 3h in CSN trial. Our findings emphasize the necessity of further evidences to confirm the ergogenic properties of CSN in connection with glycogen recovery in exercised human skeletal muscle.


2007 ◽  
Vol 103 (5) ◽  
pp. 1536-1542 ◽  
Author(s):  
Ole Hartvig Mortensen ◽  
Peter Plomgaard ◽  
Christian P. Fischer ◽  
Anne K. Hansen ◽  
Henriette Pilegaard ◽  
...  

We hypothesized that the peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) family of transcriptional coactivators (PGC-1α, PGC-1β, and PRC) is differentially regulated by training once daily vs. training twice daily every second day and that this difference might be observed in the acute response to endurance exercise. Furthermore, we hypothesized that expression levels of the PGC-1 family differ with muscular fiber-type composition. Thus, before and after 10 wk of knee extensor endurance training, training one leg once daily and the other leg twice daily every second day, keeping the total amount of training for the legs equal, skeletal muscle mRNA expression levels of PGC-1α, PGC-1β, and PRC were determined in young healthy men ( n = 7) in response to 3 h of acute exercise. No significant difference was found between the two legs, suggesting that regulation of the PGC-1 family is independent of training protocol. Training decreased PGC-1β in both legs, whereas PGC-1α was increased, but not significantly, in the leg training once daily. PRC did not change with training. Both PGC-1α and PRC were increased by acute exercise both before and after endurance training, whereas PGC-1β did not change. The mRNA levels of the PGC-1 family were examined in different types of human skeletal muscle (triceps, soleus, and vastus lateralis; n = 7). Only the expression level of PGC-1β differed and correlated inversely with percentage of type I fibers. In conclusion, there was no difference between training protocols on the acute exercise and training response of the PGC-1 family. However, training caused a decrease in PGC-1β mRNA levels.


2015 ◽  
Vol 119 (10) ◽  
pp. 1118-1126 ◽  
Author(s):  
Oliver Baum ◽  
Jennifer Gübeli ◽  
Sebastian Frese ◽  
Eleonora Torchetti ◽  
Corinna Malik ◽  
...  

The ultrastructure of capillaries in skeletal muscle was morphometrically assessed in vastus lateralis muscle (VL) biopsies taken before and after exercise from 22 participants of two training studies. In study 1 (8 wk of ergometer training), light microscopy revealed capillary-fiber (C/F) ratio (+27%) and capillary density (+16%) to be higher ( P ≤ 0.05) in postexercise biopsies than in preexercise biopsies from all 10 participants. In study 2 (6 mo of moderate running), C/F ratio and capillary density were increased (+23% and +20%; respectively, P ≤ 0.05) in VL biopsies from 6 angiogenesis responders (AR) after training, whereas 6 nonangiogenesis responders (NR) showed nonsignificant changes in these structural indicators (−4%/−4%, respectively). Forty capillary profiles per participant were evaluated by point and intersection counting on cross sections after transmission electron microscopy. In study 1, volume density (Vv) and mean arithmetic thickness (T) of endothelial cells (ECs; +19%/+17%, respectively) and pericytes (PCs; +20%/+21%, respectively) were higher ( P ≤ 0.05), whereas Vv and T of the pericapillary basement membrane (BM) were −23%/−22% lower ( P ≤ 0.05), respectively, in posttraining biopsies. In study 2, exercise-related differences between AR and NR-groups were found for Vv and T of PCs (AR, +26%/+22%, respectively, both P ≤ 0.05; NR, +1%/−3%, respectively, both P > 0.05) and BM (AR, −14%/−13%, respectively, both P ≤ 0.05; NR, −9%/−11%, respectively, P = 0.07/0.10). Vv and T of ECs were higher (AR, +16%/+18%, respectively; NR, +6% /+6%, respectively; all P ≤ 0.05) in both groups. The PC coverage was higher (+13%, P ≤ 0.05) in VL biopsies of individuals in the AR group but nonsignificantly altered (+3%, P > 0.05) in those of the NR group after training. Our study suggests that intensified PC mobilization and BM thinning are related to exercise-induced angiogenesis in human skeletal muscle, whereas training per se induces EC-thickening.


1999 ◽  
Vol 86 (6) ◽  
pp. 1828-1832 ◽  
Author(s):  
Joseph A. Houmard ◽  
D. Sean O’Neill ◽  
Donghai Zheng ◽  
Matthew S. Hickey ◽  
G. Lynis Dohm

The purpose of this study was to determine whether hyperinsulinemia alters myosin heavy chain (MHC) gene expression in human skeletal muscle. A biopsy from the vastus lateralis was obtained in young, lean [age 24.6 ± 1.0 (SE) yr, body fat 11.9 ± 1.9%, body mass index 26.1 ± 1.1 kg/m2; n = 10] men before and after 3 h of hyperinsulinemia (hyperinsulinemic-euglycemic clamp). Muscle was analyzed for mRNA of type I, IIa, and IIx MHC isoforms. Hyperinsulinemia (mean of 1,065.7 ± 9.8 pmol/l during minutes 20 to 180) did not change ( P > 0.05) the mRNA concentration of either the type I MHC or type IIA MHC isoforms. In contrast, type IIX MHC mRNA increased ( P < 0.05) with hyperinsulinemia compared with the fasted condition. These data indicate that hyperinsulinemia rapidly increases type IIx MHC mRNA in human skeletal muscle.


2000 ◽  
Vol 278 (2) ◽  
pp. E316-E329 ◽  
Author(s):  
M. G. Hollidge-Horvat ◽  
M. L. Parolin ◽  
D. Wong ◽  
N. L. Jones ◽  
G. J. F. Heigenhauser

The purpose of the study was to examine the roles of active pyruvate dehydrogenase (PDHa), glycogen phosphorylase (Phos), and their regulators in lactate (Lac−) metabolism during incremental exercise after ingestion of 0.3 g/kg of either NaHCO3 [metabolic alkalosis (ALK)] or CaCO3[control (CON)]. Subjects ( n = 8) were studied at rest, rest postingestion, and during constant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O2uptake (V˙o 2 max). Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ALK resulted in significantly ( P < 0.05) higher intramuscular Lac− concentration ([Lac−]; ALK 72.8 vs. CON 65.2 mmol/kg dry wt), arterial whole blood [Lac−] (ALK 8.7 vs. CON 7.0 mmol/l), and leg Lac− efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75%V˙o 2 max. The increased intramuscular [Lac−] resulted from increased pyruvate production due to stimulation of glycogenolysis at the level of Phos a and phosphofructokinase due to allosteric regulation mediated by increased free ADP (ADPf), free AMP (AMPf), and free Pi concentrations. PDHa increased with ALK at 60%V˙o 2 max but was similar to CON at 75%V˙o 2 max. The increased PDHa may have resulted from alterations in the acetyl-CoA, ADPf, pyruvate, NADH, and H+ concentrations leading to a lower relative activity of PDH kinase, whereas the similar values at 75% V˙o 2 max may have reflected maximal activation. The results demonstrate that imposed metabolic alkalosis in skeletal muscle results in acceleration of glycogenolysis at the level of Phos relative to maximal PDH activation, resulting in a mismatch between the rates of pyruvate production and oxidation resulting in an increase in Lac− production.


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