We evaluated the hypotheses that endurance training decreases arterial lactate concentration ([lactate](a)) during continuous exercise by decreasing net lactate release () and appearance rates (R(a)) and increasing metabolic clearance rate (MCR). Measurements were made at two intensities before [45 and 65% peak O(2) consumption (VO(2 peak))] and after training [65% pretraining VO(2 peak), same absolute workload (ABT), and 65% posttraining VO(2 peak), same relative intensity (RLT)]. Nine men (27.4 +/- 2.0 yr) trained for 9 wk on a cycle ergometer, 5 times/wk at 75% VO(2 peak). Compared with the 65% VO(2 peak) pretraining condition (4.75 +/- 0.4 mM), [lactate](a) decreased at ABT (41%) and RLT (21%) (P < 0.05). decreased at ABT but not at RLT. Leg lactate uptake and oxidation were unchanged at ABT but increased at RLT. MCR was unchanged at ABT but increased at RLT. We conclude that 1) active skeletal muscle is not solely responsible for elevated [lactate](a); and 2) training increases leg lactate clearance, decreases whole body and leg lactate production at a given moderate-intensity power output, and increases both whole body and leg lactate clearance at a high relative power output.

To evaluate the effects of endurance training on the expression of monocarboxylate transporters (MCT) in human vastus lateralis muscle, we compared the amounts of MCT1 and MCT4 in total muscle preparations (MU) and sarcolemma-enriched (SL) and mitochondria-enriched (MI) fractions before and after training. To determine if changes in muscle lactate release and oxidation were associated with training-induced changes in MCT expression, we correlated band densities in Western blots to lactate kinetics determined in vivo. Nine weeks of leg cycle endurance training [75% peak oxygen consumption (VO(2 peak))] increased muscle citrate synthase activity (+75%, P < 0.05) and percentage of type I myosin heavy chain (+50%, P < 0.05); percentage of MU lactate dehydrogenase-5 (M4) isozyme decreased (-12%, P < 0.05). MCT1 was detected in SL and MI fractions, and MCT4 was localized to the SL. Muscle MCT1 contents were consistent among subjects both before and after training; in contrast, MCT4 contents showed large interindividual variations. MCT1 amounts significantly increased in MU, SL, and MI after training (+90%, +60%, and +78%, respectively), whereas SL but not MU MCT4 content increased after training (+47%, P < 0.05). Mitochondrial MCT1 content was negatively correlated to net leg lactate release at rest (r = -0.85, P < 0.02). Sarcolemmal MCT1 and MCT4 contents correlated positively to net leg lactate release at 5 min of exercise at 65% VO(2 peak) (r = 0.76, P < 0.03 and r = 0. 86, P < 0.01, respectively). Results support the conclusions that 1) endurance training increases expression of MCT1 in muscle because of insertion of MCT1 into both sarcolemmal and mitochondrial membranes, 2) training has variable effects on sarcolemmal MCT4, and 3) both MCT1 and MCT4 participate in the cell-cell lactate shuttle, whereas MCT1 facilitates operation of the intracellular lactate shuttle.

To evaluate the hypothesis that altitude exposure and acclimatization result in increased dependency on blood glucose as a fuel, seven healthy males (23 +/- 2 yr, 72.2 +/- 1.6 kg, mean +/- SE) on a controlled diet were studied in the postabsorptive condition at sea level (SL), on acute altitude exposure to 4,300 m (AA), and after 3 wk of chronic altitude exposure to 4,300 m (CA). Subjects received a primed continuous infusion of [6,6-2D]glucose and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the SL maximal O2 consumption (VO2 max; 65 +/- 2% of altitude VO2 max). At SL, resting arterial glucose concentration was 82.4 +/- 3.2 mg/dl and rose significantly to 91.2 +/- 3.2 mg/dl during exercise. Resting glucose appearance rate (Ra) was 1.79 +/- 0.02 mg.kg-1.min-1; this increased significantly during exercise at SL to 3.71 +/- 0.08 mg.kg-1.min-1. On AA, resting arterial glucose concentration (85.8 +/- 4.1 mg/dl) was not different from sea level, but Ra (2.11 +/- 0.14 mg.kg-1.min-1) rose significantly. During exercise on AA, glucose concentration rose to levels seen at SL (91.4 +/- 3.0 mg/dl), but Ra increased more than at SL (to 4.85 +/- 0.15 mg.kg-1.min-1; P less than 0.05). Resting arterial glucose was significantly depressed with CA (70.8 +/- 3.8 mg/dl), but resting Ra increased to 3.59 +/- 0.08 mg.kg-1.min-1, significantly exceeding SL and AA values.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the effects of recombinant human GH (rhGH) in 16 men and women more than 60 yr of age. After 10 days of dietary equilibration and control collections, subjects were randomly assigned to receive 0.03, 0.06, or 0.12 mg/kg rhGH by daily injection for 7 days. A brisk rise in circulating somatomedin-C (insulin-like growth factor-I) occurred in all subjects, and this rise was dose dependent. rhGH produced striking changes in nitrogen retention, sodium excretion, and the parathyroid-vitamin D axis. Twenty-four-hour urinary nitrogen excretion decreased from 8.00 +/- 0.33 to 5.01 +/- 0.33 g (P less than 0.001), and sodium excretion decreased from 45.9 +/- 2.96 to 21.2 +/- 3.48 mmol/day (P less than 0.001). Serum calcium concentrations did not change, but serum inorganic phosphorus levels of 1.08 +/- 0.04 mmol/L at baseline increased significantly after rhGH treatment to 1.33 +/- 0.04 mmol/L (P less than 0.001). Increases were also observed in circulating PTH (53.2 +/- 6 vs. 39.5 +/- 4.2 ng/L; P less than 0.01) and calcitriol (82.8 vs. 65.8 pmol/L; P less than 0.05). A rise in serum osteocalcin (10.3 +/- .86 vs. 8.0 +/- 0.5 micrograms/L; P less than 0.05) was accompanied by increased urinary excretion of hydroxyproline (628 +/- 63 vs. 406 +/- 44 mumol/day; P less than 0.01). Despite the reduction in sodium excretion, marked increases were observed in urinary calcium (6.04 +/- 0.97 vs. 3.27 +/- 0.40 mmol/day; P less than 0.01). rhGH significantly impaired oral glucose tolerance and reduced insulin sensitivity, but was otherwise well tolerated and produced no systematic changes in weight or blood pressure. The results of this study indicate that rhGH requires further study as a potential agent for attenuating or reversing the loss of muscle and bone in elderly people.

The hypothesis that high-altitude weight loss can be prevented by increasing energy intake to meet energy requirement was tested in seven men, 23.7 +/- 4.3 (SD) yr, taken to 4,300 m for 21 days. Energy intake required to maintain body weight at sea level was found to be 3,118 +/- 300 kcal/day, as confirmed by nitrogen balance. Basal metabolic rate (BMR), determined by indirect calorimetry, increased 27% on day 2 at altitude and then decreased and reached a plateau at 17% above the sea level BMR by day 10. Energy expended during strenuous activities was 37% lower at altitude than at sea level. Fecal excretion of energy, nitrogen, total fiber, and total volatile fatty acids was not significantly affected by altitude. Energy intake at altitude was adjusted after 1 wk, on the basis of the increased BMR, to 3,452 +/- 452 kcal/day. Mean nitrogen balance at altitude was negative (-0.25 +/- 0.71 g/day) before energy intake was adjusted but rose significantly thereafter (0.20 +/- 0.71 and 0.44 +/- 0.66 g/day during weeks 2 and 3). Mean body weight decreased 2.1 +/- 1.0 kg over the 3 wk of the study, but the rate of weight loss was significantly diminished after the increase in energy intake (201 +/- 75 vs. 72 +/- 48 g/day). Individual regression lines drawn through 7-day segments of body weight showed that in four of seven subjects the slopes of body weight were not significantly different from zero after the 2nd wk. Thus weight loss ceased in four of seven men in whom increased BMR at altitude was compensated with increased energy intake.(ABSTRACT TRUNCATED AT 250 WORDS)