Taisuke Enoki

We investigated the effects of nightly intermittent exposure to hypoxia and of training during intermittent hypoxia on both erythropoiesis and running economy (RE), which is indicated by the oxygen cost during running at submaximal speeds. Twenty-five college long-and middle-distance runners [maximal oxygen uptake (Vo(2max)) 60.3 +/- 4.7 ml.kg(-1).min(-1)] were randomly assigned to one of three groups: hypoxic residential group (HypR, 11 h/night at 3,000 m simulated altitude), hypoxic training group (HypT), or control group (Con), for an intervention of 29 nights. All subjects trained in Tokyo (altitude of 60 m) but HypT had additional high-intensity treadmill running for 30 min at 3,000 m simulated altitude on 12 days during the night intervention. Vo(2) was measured at standing rest during four submaximal speeds (12, 14, 16, and 18 km/h) and during a maximal stage to volitional exhaustion on a treadmill. Total hemoglobin mass (THb) was measured by carbon monoxide rebreathing. There were no significant changes in Vo(2max), THb, and the time to exhaustion in all three groups after the intervention. Nevertheless, HypR showed similar to 5% improvement of RE in normoxia (P < 0.01) after the intervention, reflected by reduced Vo(2) at 18 km/h and the decreased regression slope fitted to Vo(2) measured during rest position and the four submaximal speeds (P < 0.05), whereas no significant corresponding changes were found in HypT and Con. We concluded that our dose of intermittent hypoxia (3,000 m for similar to 11 h/night for 29 nights) was insufficient to enhance erythropoiesis or Vo(2max), but improved the RE at race speed of college runners.

We have examined the effects of administration of testosterone for 7 days on monocarboxylate transporter (MCT) 1 and MCT4 mRNAs and proteins in seven metabolically heterogeneous rat hindlimb muscles and in the heart. In addition, we also examined the effects of testosterone treatment on plasmalemmal MCT1 and MCT4, and lactate transport into giant sarcolemmal vesicles prepared from red and white hindlimb muscles and the heart. Testosterone did not alter MCT1 or MCT4 mRNA, except in the plantaris muscle. Testosterone increased MCT1 (20%-77%, P < 0.05) and MCT4 protein (29%-110%, P < 0.05) in five out of seven muscles examined. In contrast, in the heart MCT1 protein was not increased (P > 0.05), and MCT 4 mRNA and protein were not detected. There was no correlation between the testosterone-induced increments in MCT1 and MCT4 proteins. Muscle fibre composition was not associated with testosterone-induced increments in MCT1 protein. In contrast, there was a strong positive relationship between the testosterone-induced increments in MCT4 protein and the fast-twitch fibre composition of rat muscles. Lactate transport into giant sarcolemmal vesicles was increased in red (23%, P < 0.05) and white muscles (21%, P < 0.05), and in the heart (58%, P < 0.05) of testosterone-treated animals (P < 0.05). However, plasmalemmal MCT1 protein (red, +40%, P < 0.05; white, +39%, P < 0.05) and plasmalemmal MCT4 protein (red, +25%, P < 0.05; white, +48%, P < 0.05) were increased only in skeletal muscle. In the heart, plasmalemmal MCT1 protein was reduced (-20%, P < 0.05). In conclusion, these studies have shown that testosterone induces an increase in both MCT1 and MCT4 proteins and their plasmalemmal content in skeletal muscle. However, the testosterone-induced effect was tissue-specific, as MCT1 protein expression was not altered in the heart. In the heart, the testosterone-induced increase in lactate transport cannot be explained by changes in plasmalemmal MCT1 content, but in skeletal muscle the increase in the rate of lactate transport was associated with increases in plasmalemmal MCT1 and MCT4.

We examined whether the quantity of exercise performed influences the expression of monocarboxylate transporter (MCT) 1 and MCT4 in mouse skeletal muscles (plantaris, tibialis anterior, soleus) and heart. Wheel running exercise (1, 3, and 6 wk) was used, which results in marked variations in self-selected running activity. Differences in muscle MCT1 and MCT4 among animals, before the initiation of running, were not related to the quantity of exercise performed on the first day of wheel running. No changes in MCT4 were observed over the Course of the study (P > 0.05). After 6 wk of running, were there significant increases in heart (50%; P < 0.05) and muscle MCT1 (31-60%; P < 0.05) but not after I and 3 wk (P > 0.05). Because skeletal muscle MCT1 and running distances varied considerably, we examined the relationship between these two parameters. Within the first week of training, MCTI was negatively correlated with the accumulated running distance (r = -0.70, P < 0.05). On further analysis, it appears that, in the first week, excessive running (>20 km/wk) represses MCTI (-16.1%; P < 0.05), whereas more modest amounts of running (<20 km/wk) increase MCTI (+37%; P < 0.05). After 3 wk of running, a positive relationship was observed between MCTI and running distance (r = +0.76), although there is a threshold that must be exceeded before an increase over the control animals occurs. Finally, in week 6, when MCTI was increased in the tibialis anterior and plantaris muscles, there were no correlations with the accumulated running distances. These studies have shown that mild exercise training fails to increase MCT4 and that changes in MCT1 are complex, depending not only the accumulated exercise but also on the stage of training.

We compared the changes in monocarboxylate transporter 1 ( MCT1) and 4 (MCT4) proteins in heart and skeletal muscles in sedentary control and streptozotocin (STZ)-induced diabetic rats ( 3 wk) and in trained ( 3 wk) control and STZ-induced diabetic animals. In nondiabetic animals, training increased MCT1 in the plantaris (+51%; P < 0.01) but not in the soleus (+9%) or the heart (+14%). MCT4 was increased in the plantaris (+ 48%; P < 0.01) but not in the soleus muscles of trained nondiabetic animals. In sedentary diabetic animals, MCT1 was reduced in the heart ( - 30%), and in the plantaris ( - 31%; P < 0.01) and soleus ( - 26%) muscles. MCT4 content was also reduced in sedentary diabetic animals in the plantaris ( - 52%; P < 0.01) and soleus ( - 25%) muscles. In contrast, in trained diabetic animals, MCT1 and MCT4 in heart and/or muscle were similar to those of sedentary, nondiabetic animals ( P > 0.05) but were markedly greater than in the sedentary diabetic animals [ MCT1: plantaris +63%, soleus +51%, heart +51% ( P > 0.05); MCT4: plantaris +107%, soleus +17% ( P > 0.05)]. These studies have shown that 1) with STZ-induced diabetes, MCT1 and MCT4 are reduced in skeletal muscle and/or the heart and 2) exercise training alleviated these diabetes-induced reductions.