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

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 (W(max))] 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 ≤ 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 ≤ 0.05) before bed rest than after. Muscle glycogen content tended to be higher (0.05< P ≤ 0.10) after bed rest than before, but muscle glycogen breakdown in response to exercise was similar before and after bed rest. PDH-E1α protein content did not change in response to bed rest or in response to the exercise intervention. Exercise increased (P ≤ 0.05) the activity of PDH in the active form (PDHa) and induced (P ≤ 0.05) dephosphorylation of PDH-E1α on Ser2?3, Ser2?? and Ser3??, with no difference before and after bed rest. In conclusion, although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed. This suggests that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant (e.g., insulin resistant) individuals.     

Exercise adaptation attenuates VEGF gene expression in human skeletal muscle

Angiogenesis is a component of the multifactoral adaptation to exercise training, and vascular endothelial growth factor (VEGF) is involved in extracellular matrix changes and endothelial cell proliferation. However, there is limited evidence supporting the role of VEGF in the exercise training response. Thus we studied mRNA levels of VEGF, using quantitative Northern analysis, in untrained and trained human skeletal muscle at rest and after a single bout of exercise. Single leg knee-extension provided the acute exercise stimulus and the training modality. Four biopsies were collected from the vastus lateralis muscle at rest in the untrained and trained conditions before and after exercise. Training resulted in a 35% increase in muscle oxygen consumption and an 18% increase in number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were similar before (0.38 +/- 0.04) and after (1.2 +/- 0.4) training. When muscle was untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 +/- 6.7). The VEGF/18S mRNA response to acute exercise in the trained state was markedly attenuated (5.4 +/- 1.3). These data support the concept that VEGF is involved in exercise-induced skeletal muscle angiogenesis and appears to be subject to a negative feedback mechanism as exercise adaptations occur.     

Antioxidant supplementation enhances the exercise-induced increase in mitochondrial uncoupling protein 3 and endothelial nitric oxide synthase mRNA content in human skeletal muscle

The effects of acute exercise on the mRNA content of selected genes were examined during control conditions and after oral intake of antioxidants. In addition, to provide evidence for formation of reactive oxygen species (ROS) in human skeletal muscle during exercise, cytochrome c reduction was measured in microdialysate from the muscle. For the study on the effects of antioxidants on mRNA content, seven healthy, habitually active, male subjects participated in a double-blinded experimental design in which they, on one occasion, received a placebo and, on another, a mixture of antioxidants containing 1500 mg vitamin C, 120 mg coenzyme Q, and 345 mg alpha-tocopherol every day for 7 days before the experiment. On the experimental day the subjects cycled for 90 min and muscle biopsies were taken preexercise and at 1, 3, and 5 h after exercise. Exercise induced an increase in the eNOS, UCP3, PGC-1alpha, VEGF, Hsp72, and HO-1 mRNA content (p < 0.001), whereas there was no change in the Hsc70 mRNA level. Prior antioxidant treatment further enhanced (p < 0.05) the eNOS and UCP3 mRNA content after exercise. Moreover, the overall level of Hsc70 mRNA tended (p = 0.07) to be higher after antioxidant treatment. In another group of healthy male subjects, cytochrome c reduction was determined in microdialysate from the thigh muscle at rest and during knee extensor exercise to determine ROS formation. There was a significant increase in cytochrome c reduction with exercise both at 14 ( approximately 25%) and at 30 W ( approximately 50%). The data show that ROS are formed within skeletal muscle during exercise and that oral intake of antioxidants can enhance the exercise-induced adaptive mRNA responses of eNOS and UCP3.     

A single bout of exercise activates matrix metalloproteinase in human skeletal muscle.

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.     

Effect of short-term exercise training on angiogenic growth factor gene responses in rats.

We investigated whether 1) 5 days of exercise training would reduce the acute exercise-induced increase in skeletal muscle growth factor gene expression; and 2) reductions in the increase in growth factor gene expression in response to short-term exercise training would be coincident with increases in skeletal muscle oxidative potential. Female Wistar rats were used. Six groups (rest; exercise for 1-5 consecutive days) were used to measure the growth factor response through the early phases of an exercise training program. Vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Citrate synthase activity was analyzed from the right gastrocnemius. VEGF and TGF-beta1 mRNA increased after each of 5 days of exercise training, whereas exercise on any day did not increase bFGF mRNA. On day 1, the VEGF mRNA response was significantly greater than on days 2-5. However, the reduced increase in VEGF mRNA observed on days 2-5 was not coincident with increases in citrate synthase activity. These findings suggest that, in skeletal muscle, 1) VEGF and TGF-beta1 mRNA are increased through 5 days of exercise training and 2) the reduced exercise-induced increase in VEGF mRNA responses on days 2-5 does not result from increases in oxidative potential.     

Lower capillarization, VEGF protein, and VEGF mRNA response to acute exercise in the vastus lateralis muscle of aged vs. young women.

In humans, the majority of studies demonstrate an age-associated reduction in the number of capillaries surrounding skeletal muscle fibers; however, recent reports in rats suggest that muscle capillarization is well maintained with advanced age. In sedentary and trained men, aging lowers the number of capillaries surrounding type II, but not type I, skeletal muscle fibers. The fiber type-specific effect of aging on muscle capillarization is unknown in women. Vascular endothelial growth factor (VEGF) is important in the basal maintenance of skeletal muscle capillarization, and lower VEGF expression is associated with increased age in nonskeletal muscle tissue of women. Compared with young women (YW), we hypothesized that aged women (AW) would demonstrate 1) lower muscle capillarization in a fiber type-specific manner and 2) lower VEGF and VEGF receptor expression at rest and in response to acute exercise. Nine sedentary AW (70 + 8 yr) and 11 YW (22 + 3 yr) had vastus lateralis muscle biopsies obtained before and at 4 h after a submaximal exercise bout for the measurement of morphometry and VEGF and VEGF receptor expression. In AW compared with YW, muscle capillary contacts were lower overall (YW: 2.36 + 0.32 capillaries; AW: 2.08 + 0.17 capillaries), specifically in type II (YW: 2.37 + 0.39 capillaries; AW: 1.91 + 0.36 capillaries) but not type I fibers (YW: 2.36 + 0.34 capillaries; AW: 2.26 + 0.24 capillaries). Muscle VEGF protein was 35% lower at rest, and the exercise-induced increase in VEGF mRNA was 50% lower in AW compared with YW. There was no effect of age on VEGF receptor expression. These results provide evidence that, in the vastus lateralis of women, 1) capillarization surrounding type II muscle fibers is lower in AW compared with YW and 2) resting VEGF protein and the VEGF mRNA response to exercise are lower in AW compared with YW.     

Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest.

This study assessed the effects of inactivity on GLUT-4 content of human skeletal muscle and evaluated resistance training as a countermeasure to inactivity-related changes in GLUT-4 content in skeletal muscle. Nine young men participated in the study. For 19 days, four control subjects remained in a -6 degrees head-down tilt at all times throughout bed rest, except for showering every other day. Five training group subjects also remained at bed rest, except during resistance training once in the morning. The resistance training consisted of 30 isometric maximal voluntary contractions for 3 s each; leg-press exercise was used to recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were allowed between bouts of maximal contraction. Muscle biopsy samples were obtained from the lateral aspect of vastus lateralis (VL) muscle before and after the bed rest. GLUT-4 content in VL muscle of the control group was significantly decreased after bed rest (473 +/- 48 vs. 398 +/- 66 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively), whereas GLUT-4 significantly increased in the training group with bed rest (510 +/- 158 vs. 663 +/- 189 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively). The present study demonstrated that GLUT-4 in VL muscle decreased by approximately 16% after 19 days of bed rest, and isometric resistance training during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.     

Effect of acute exercise and exercise training on VEGF splice variants in human skeletal muscle

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to approximately 70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF(165) mRNA. Acute exercise induced an increase (P < 0.05) in total VEGF mRNA levels as well as VEGF(165) and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg (P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF(165) mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF(165) mRNA.     

Endurance training reduces the contraction-induced interleukin-6 mRNA expression in human skeletal muscle

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men (n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher (P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold (P < 0.05) in response to exercise before the training period, but only 8-fold (P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 (P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.     

Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans.

Increased levels of reactive oxygen and nitrogen species, as seen in response to exercise, challenge the cellular integrity. Important protective adaptive changes include induction of heat shock proteins (HSPs). We hypothesized that supplementation with antioxidant vitamins C (ascorbic acid) and E (tocopherol) would attenuate the exercise-induced increase of HSP72 in the skeletal muscle and in the circulation. Using randomization, we allocated 21 young men into three groups receiving one of the following oral supplementations: RRR-alpha-tocopherol 400 IU/day + ascorbic acid (AA) 500 mg/day (CEalpha), RRR-alpha-tocopherol 290 IU/day + RRR-gamma-tocopherol 130 IU/day + AA 500 mg/day (CEalphagamma), or placebo (Control). After 28 days of supplementation, the subjects performed 3 h of knee extensor exercise at 50% of the maximal power output. HSP72 mRNA and protein content was determined in muscle biopsies obtained from vastus lateralis at rest (0 h), postexercise (3 h), and after a 3-h recovery (6 h). In addition, blood was sampled for measurements of HSP72, alpha-tocopherol, gamma-tocopherol, AA, and 8-iso-prostaglandin-F2alpha (8-PGF2alpha). Postsupplementation, the groups differed with respect to plasma vitamin levels. The marker of lipid peroxidation, 8-iso-PGF2alpha, increased from 0 h to 3 h in all groups, however, markedly less (P < 0.05) in CEalpha. In Control, skeletal muscle HSP72 mRNA content increased 2.5-fold (P < 0.05) and serum HSP72 protein increased 4-fold (P < 0.05) in response to exercise, whereas a significant increase of skeletal muscle HSP72 protein content was not observed (P = 0.07). In CEalpha, skeletal muscle HSP72 mRNA, HSP72 protein, and serum HSP72 were not different from Control in response to exercise. In contrast, the effect of exercise on skeletal muscle HSP72 mRNA and protein, as well as circulating HSP72, was completely blunted in CEalphagamma. The results indicate that gamma-tocopherol comprises a potent inhibitor of the exercise-induced increase of HSP72 in skeletal muscle as well as in the circulation.     

The critical role of VEGF in skeletal muscle angiogenesis and blood flow

VEGF (vascular endothelial growth factor) is well known as an important molecule in angiogenesis. Its inhibition is pursued as an anticancer therapy; its enhancement as therapy for tissue ischaemia. In the present paper, its role in skeletal muscle is explored, both at rest and after exercise. Muscle VEGF mRNA and protein are increased severalfold after heavy exercise. Whereas global VEGF knockout is embryonically lethal, muscle-specific knockout is not, providing models for studying its functional significance. Its deletion in adult mouse skeletal muscle: (i) reduces muscle capillarity by more than 50%, (ii) decreases exercise endurance time by approximately 80%, and (iii) abolishes the angiogenic response to exercise training. What causes VEGF to increase with exercise is not clear. Despite regulation by HIF (hypoxia-inducible factor), increased HIF on exercise, and PO2 falling to single digit values during exercise, muscle-specific HIF knockout does not impair performance or capillarity, leaving many unanswered questions.     

Exercise induces an increase in muscle UCP3 as a component of the increase in mitochondrial biogenesis

Previous studies have indicated that exercise acutely induces large increases in uncoupling protein-3 (UCP3) in skeletal muscle, whereas endurance training results in marked decreases in muscle UCP3. Because UCP3 expression appears to be regulated by the same mechanism as other mitochondrial constituents, it seemed unlikely that exercise would result in such large and divergent changes in mitochondrial composition. The purpose of this study was to test the hypothesis that major changes in UCP3 protein concentration do not occur independently of mitochondrial biogenesis and that UCP3 increases as a component of the exercise-induced increase in mitochondria. We found a large increase in UCP3 mRNA immediately and 3 h after a bout of swimming. UCP3 protein concentration was increased approximately 35% 18 h after a single exercise bout, approximately 63% after 3 days, and approximately 84% after 10 days of exercise. These increases in UCP3 roughly paralleled those of other mitochondrial marker proteins. Our results are consistent with the interpretation that endurance exercise induces an adaptive increase in mitochondria that have a normal content of UCP3.     

Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans

Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P < 0.05 vs. before bed rest) and reduced the maximal voluntary force of plantar flexion by 15%. In contrast, bed rest did not alter the increase in MSNA response to fatiguing handgrip and had no effects on the maximal voluntary force of handgrip. Although PEMI sustained MSNA activation before bed rest in all trials, bed rest entirely eliminated the PEMI-induced increase in MSNA in leg exercises but partially attenuated it in forearm exercises. These results do not support our hypothesis but indicate that bed rest causes a reduction in isometric exercise-induced sympathetic activation in (probably atrophied) antigravity leg muscles.     

Sirtuin 1 (SIRT1) deacetylase activity is not required for mitochondrial biogenesis or peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) deacetylation following endurance exercise

The protein deacetylase, sirtuin 1 (SIRT1), is a proposed master regulator of exercise-induced mitochondrial biogenesis in skeletal muscle, primarily via its ability to deacetylate and activate peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). To investigate regulation of mitochondrial biogenesis by SIRT1 in vivo, we generated mice lacking SIRT1 deacetylase activity in skeletal muscle (mKO). We hypothesized that deacetylation of PGC-1α and mitochondrial biogenesis in sedentary mice and after endurance exercise would be impaired in mKO mice. Skeletal muscle contractile characteristics were determined in extensor digitorum longus muscle ex vivo. Mitochondrial biogenesis was assessed after 20 days of voluntary wheel running by measuring electron transport chain protein content, enzyme activity, and mitochondrial DNA expression. PGC-1α expression, nuclear localization, acetylation, and interacting protein association were determined following an acute bout of treadmill exercise (AEX) using co-immunoprecipitation and immunoblotting. Contrary to our hypothesis, skeletal muscle endurance, electron transport chain activity, and voluntary wheel running-induced mitochondrial biogenesis were not impaired in mKO versus wild-type (WT) mice. Moreover, PGC-1α expression, nuclear translocation, activity, and deacetylation after AEX were similar in mKO versus WT mice. Alternatively, we made the novel observation that deacetylation of PGC-1α after AEX occurs in parallel with reduced nuclear abundance of the acetyltransferase, general control of amino-acid synthesis 5 (GCN5), as well as reduced association between GCN5 and nuclear PGC-1α. These findings demonstrate that SIRT1 deacetylase activity is not required for exercise-induced deacetylation of PGC-1α or mitochondrial biogenesis in skeletal muscle and suggest that changes in GCN5 acetyltransferase activity may be an important regulator of PGC-1α activity after exercise.     

Vascular endothelial growth factor mRNA expression and arteriovenous balance in response to prolonged,submaximal exercise in humans

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.     

2-D DIGE analysis of the mitochondrial proteome from human skeletal muscle reveals time course-dependent remodelling in response to 14 consecutive days of endurance exercise training

Adaptation of skeletal muscle to repeated bouts of endurance exercise increases aerobic capacity and improves mitochondrial function. However, the adaptation of human skeletal muscle mitochondrial proteome to short‐term endurance exercise training has not been investigated. Eight sedentary males cycled for 60 min at 80% of peak oxygen consumption (VO_2peak) each day for 14 consecutive days, resulting in an increase in VO_2peak of 17.5±3.8% (p<0.01). Mitochondria‐enriched protein fractions from skeletal muscle biopsies taken from m. vastus lateralis at baseline, and on the morning following the 7th and 14th training sessions were subjected to 2‐D DIGE analysis with subsequent MS followed by database interrogation to identify the proteins of interest. Thirty‐one protein spots were differentially expressed after either 7 or 14 days of training (ANOVA, p<0.05). These proteins included subunits of the electron transport chain, enzymes of the tricarboxylic acid cycle, phosphotransfer enzymes, and regulatory factors in mitochondrial protein synthesis, oxygen transport, and antioxidant capacity. Several proteins demonstrated a time course‐dependent induction during training. Our results illustrate the phenomenon of skeletal muscle plasticity with the extensive remodelling of the mitochondrial proteome occurring after just 7 days of exercise training suggestive of enhanced capacity for adenosine triphosphate generation at a cellular level.     

Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes

Low-volume high-intensity interval training (HIT) is emerging as a time-efficient exercise strategy for improving health and fitness. This form of exercise has not been tested in type 2 diabetes and thus we examined the effects of low-volume HIT on glucose regulation and skeletal muscle metabolic capacity in patients with type 2 diabetes. Eight patients with type 2 diabetes (63 ± 8 yr, body mass index 32 ± 6 kg/m(2), Hb(A1C) 6.9 ± 0.7%) volunteered to participate in this study. Participants performed six sessions of HIT (10 × 60-s cycling bouts eliciting ～90% maximal heart rate, interspersed with 60 s rest) over 2 wk. Before training and from ～48 to 72 h after the last training bout, glucose regulation was assessed using 24-h continuous glucose monitoring under standardized dietary conditions. Markers of skeletal muscle metabolic capacity were measured in biopsy samples (vastus lateralis) before and after (72 h) training. Average 24-h blood glucose concentration was reduced after training (7.6 ± 1.0 vs. 6.6 ± 0.7 mmol/l) as was the sum of the 3-h postprandial areas under the glucose curve for breakfast, lunch, and dinner (both P < 0.05). Training increased muscle mitochondrial capacity as evidenced by higher citrate synthase maximal activity (～20%) and protein content of Complex II 70 kDa subunit (～37%), Complex III Core 2 protein (～51%), and Complex IV subunit IV (～68%, all P < 0.05). Mitofusin 2 (～71%) and GLUT4 (～369%) protein content were also higher after training (both P < 0.05). Our findings indicate that low-volume HIT can rapidly improve glucose control and induce adaptations in skeletal muscle that are linked to improved metabolic health in patients with type 2 diabetes.     

Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise.

The exercise-induced expression of heat shock proteins (HSPs) in rodent models is relatively well defined. In contrast, comparable data from human studies are limited and the exercise-induced stress response of human skeletal muscle is far from understood. This study has characterized the time course and magnitude of the HSP response in the skeletal muscles of a healthy active, but untrained, young male population following a running exercise protocol. Eight subjects performed 45 min of treadmill running at a speed corresponding to their lactate threshold (11.7 +/- 0.5 km/h; 69.8 +/- 4.8% maximum O2 uptake). Muscle biopsies were obtained from the vastus lateralis muscle immediately before and at 24 h, 48 h, 72 h, and 7 days postexercise. Exercise induced a significant (P < 0.05) but variable increase in HSP70, heat shock cognate (HSC) 70, and HSP60 expression with peak increases (typically occurring at 48 h postexercise) to 210, 170, and 139% of preexercise levels, respectively. In contrast, exercise did not induce a significant increase in either HSP27, alphaB-crystallin, SOD 2 (MnSOD) protein content, or the activity of SOD and catalase. When examining baseline protein levels, HSC70, HSP27, and alphaB-crystallin appeared consistently expressed between subjects, whereas HSP70 and MnSOD displayed marked individual variation of up to 3- and 1.5-fold, respectively. These data are the first to define the time course and extent of HSP production in human skeletal muscle following a moderately demanding and nondamaging running exercise protocol. Data demonstrate a differential effect of aerobic exercise on specific HSPs.