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J Appl Physiol 96: 747-753, 2004. First published October 31, 2003; doi:10.1152/japplphysiol.00711.2003
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Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men

Jill A. Kanaley,1 Rolf Dall,2 Niels Møller,2 Sven C. Nielsen,3 Jens Sandahl Christiansen,2 Michael D. Jensen,4 and Jens Otto Lunde Jørgensen2

1Department of Exercise Science, Syracuse University, Syracuse, New York 13244; 2Medical Department M (Endocrinology and Diabetes), 3Department of Respiratory Diseases and Institute of Experimental Clinical Research, Aarhus University Hospital, DK 5000 Aarhus, Denmark; and 4Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905

Submitted 9 July 2003 ; accepted in final form 23 October 2003


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 ± 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 ± 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 ± 26 vs. 168 ± 28 µmol/min, P < 0.05) and remained elevated throughout recovery (P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 ± 14 µmol/min), but the recovery flux was greater on the +GH day than in the controls (169 ± 17 vs. 119 ± 11 µmol/min, respectively, P < 0.01). A significant time effect (P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.

lipolysis; glucose turnover; protein turnover; growth hormone

IN RESPONSE TO EXERCISE, there are perturbations in the hormonal and metabolic milieu, such that with increasing exercise duration there is a transition to greater free fatty acid (FFA) utilization. This shift in substrate utilization is coordinated by an increase in catecholamines and a decrease in insulin levels (11, 19), with concomitant changes in cortisol, growth hormone (GH), and glucagon. In particular, in most individuals, there is a dramatic exercise-induced GH increase (15, 16, 30), yet the physiological significance of this increase has not been clearly elucidated. At rest, a GH infusion in healthy individuals increases lipolysis with maximal elevations after 120-160 min (24), and there is decreased oxidative glucose disposal and protein retention (6, 8, 23-25). Furthermore, in viscerally obese men, low doses of recombinant GH increases lipolysis but does not alter glucose and protein turnover rates (18).

During exercise, GH is presumed to stimulate lipid utilization, inhibit glucose oxidation, and stimulate protein synthesis, but this has so far not been experimentally tested (3). Studies comparing GH-deficient adults with healthy subjects or studies using somatostatin have found no effect of GH on fat metabolism at rest (5, 13). In GH-deficient adults, withdrawal of GH for 3 mo resulted in reductions in the release and uptake of lipid intermediates during moderately intense exercise (10). Previous work (1) has demonstrated that long-term recombinant human GH administration increases sensitivity to the lipolytic effect of epinephrine in abdominal subcutaneous adipose tissue. This was speculated to be due to a greater {beta}-adrenergic pathway efficiency. Although chronic removal of GH may impact lipolysis during exercise, it is unclear whether acute GH exposure stimulates lipolysis in GH-deficient adults.

The present study was designed to examine the effects of acute GH exposure on lipid, glucose, and protein metabolism during and after moderate-intensity aerobic exercise. As a model, we studied GH-deficient men receiving chronic GH substitution during exercise with and without a concomitant intravenous GH bolus. GH administration was designed to mimic the GH pattern normally observed in healthy individuals, and for comparison we also included a control group of untreated healthy subjects. We hypothesized that GH administration would augment lipid metabolism during exercise and that the absence of GH during exercise would cause perturbations in lipid, glucose, and protein metabolism.


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
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Subjects and experimental design. The study population consisted of 16 men [8 GH-deficient and 8 healthy men (controls)], who provided voluntary oral and written informed consent, and the study was approved by the regional ethics committee of Aarhus Kommunehospital. The patients all had organic pituitary disease and had previously been diagnosed as GH deficient by an arginine infusion, insulin tolerance test, or both. GH-deficient subjects had to be between 18 and 55 yr of age, GH deficient for at least 12 mo, and receiving GH replacement at a stable dose for at least 12 mo. Table 1 lists the medications the GH-deficient subjects were taking and their normal dose of GH. The controls were matched for age, and both groups were only moderately active.


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  		Table 1. Clinical characteristics of the GH-deficient subjects

 

Each GH-deficient subject was examined on three occasions, and the control subjects were studied on two occasions. On the first visit, all subjects underwent a test of their peak aerobic capacity on the cycle ergometer to establish their level of cardiovascular fitness [peak oxygen consumption (O2 peak)] and lactate threshold, and they had their body composition assessed. The GH-deficient subjects were then evaluated on two occasions (separated by 1 mo) for an 8-h period. On both occasions, the subjects exercised for 45 min at an initial intensity equivalent to their lactate threshold. On the study day of exercise without GH (-GH), the patients did not take their prescribed GH injection the evening before. During the exercise study with GH (+GH), the GH injection was taken the evening before, and an intravenous GH infusion was administered during exercise (0.4 IU norditropin; Novo Nordisk, Bagsværd, Denmark) (24). These study days were conducted in a randomized order. The control subjects were studied on one occasion with an identical protocol to the GH-deficient adults but without receiving GH.

O2 peak. O2 peak was determined by using a continuous cycle ergometer protocol. Subjects started cycling at 100 W for the first 3 min, and the power output was increased by 25 W every 3 min until volitional fatigue. Oxygen consumption was measured throughout the study by using indirect calorimetry (MedGraphics CPX, St. Paul, MN). O2 peak was selected as the highest oxygen consumption or where a further power output increase resulted in less than a 200-ml increase in oxygen. In addition, all subjects had a rating of perceived exertion of >18 on the Borg scale and a respiratory exchange ratio (RER) of >1.0, and all subjects reached their age-predicted maximal heart rate (20). Blood lactate samples were taken at the end of every 3-min stage to determine the lactate threshold. The individual lactate threshold was selected as the point before the nonlinear increase in lactate levels. Body composition was assessed by using dual-energy X-ray absorptiometry (Hologic QDR 2000, version 5.54).

Study days. On a study day, subjects reported to the Clinical Research Center at 0700, at which time a catheter was placed in a dorsal hand vein and was heated for obtaining arterialized samples, and in the antecubital vein for infusions. Subjects remained in the supine position throughout the study except for the 45 min of exercise. Resting blood samples were taken for 3 h before exercise [time (t) = -180, -60, -30, -15, and 0 min], during exercise (t = 15, 30, and 45 min), and during 2.75 h of recovery (t = 60, 90, 120, 180, 210, 225, and 240 min). During exercise, subjects cycled at a power output that was equivalent to their individual lactate threshold [mean lactate concentration at the onset of exercise was ~2.2 mM (~62% of O2 peak)] for 45 min on the cycle ergometer. The GH-deficient adults exercised at a power output of 120.0 ± 6.0 W and the controls at 155.1 ± 8.3 W. On the +GH day, 0.4 mg IU GH was administered after the start of exercise (1/5 administered every 5 min: t = 5, 10, 15, 20, and 25 min). On completion of exercise, subjects again remained in the supine position. All resting and recovery samples were taken with the subject in the supine position, and the exercise samples were taken with the subject sitting upright.

Indirect calorimetry (Deltatrac monitor, Datex Instrumentarium, Helsinki, Finland) was performed for 30 min (initiated at time = -60 and time = 135). Forearm blood flow was taken before each sample by means of venous occlusion plethysmography (34). A wrist cuff was inflated to a pressure of 250 mmHg to interrupt hand blood flow immediately before each forearm flow determination.

Tracer measurements. Beginning at 0730, priming doses of L-[15N]phenylalanine (0.7 mg/kg), L-[2H4]tyrosine (0.5 mg/kg), L-[15N]tyrosine (0.5 mg/kg) (Cambridge Isotope Laboratories), and [3-H3]glucose bolus (15 µCi; New England Nuclear, Boston, MA) were administered to establish a rapid plateau. This was immediately followed by a continuous infusion of L-[15N]phenylalanine (0.7 mg · kg-1 · h-1), L-[2H4]tyrosine (0.5 mg · kg-1 · h-1), and [3-3H]glucose (0.12 mCi/min) throughout the 7-h study period. [9,10-3H]palmitate (0.25 µCi/min) was given as a continuous infusion for 2 h before and during exercise and for the last 2 h of the study period. Chemical and isotopic purity was tested in these isotopes before use, and all solutions were prepared under sterile conditions and were free of bacteria and pyrogens before use. [9,10-3H]palmitate specific activity (21) and tritiated glucose (22) were measured by methods previously described. Electron ionization conditions were used to measure the t-butyldimethylsilyl ether derivatives of L-[15N]phenylalanine, L-[2H4]tyrosine, and L-[N15]tyrosine (26). Plasma amino acid concentrations were determined by using high-performance liquid chromatography, with precolumn o-phthalaldehyde derivatization (14). Concentration of phenylalanine and tyrosine were measured by mass spectrometry using {beta}-methylphenylalanine and {alpha}-methyltyrosine, respectively, as internal standards (26). Plasma glucose concentrations were measured in duplicate immediately after sampling on a glucose analyzer (Beckman Instruments, Palo Alto, CA). Serum GH levels were measured with a double monoclonal immunofluorometric assay (Delfia, Wallac, Finland), whereas plasma glucagon levels (28) and serum C-peptide (Immunoclear, Stillwater, MN) were measured by radioimmunoassay techniques. The intra-assay coefficient of variation was <5% (range 0.03-200 mU/l), and the lower detection limit was <0.06 mU/l for the GH assay. A commercial enzyme-linked immunosorbent assay (Dako, Glostrup, Denmark) was used for insulin levels (28), and catecholamines were measured by liquid chromatography (7). Urea excretion was determined by an indophenol method and serum urea by a commercial kit (Cobas Integra, Roche, Hvidovre, Denmark). FFA were determined by a colorimetric method using a commercial kit (Wako Chemicals, Neuss, Germany).

Tracer kinetics. For the measurement of whole body phenylalanine kinetics, the equations of Thompson et al. (32) were used. Phenylalanine flux and tyrosine flux were calculated as previously reported (27). Glucose rate of appearance (Ra) and disappearance (Rd) were calculated as described by Møller et al. (22). Palmitate flux was determined by using steady-state equations previously described (12). The palmitate values are expressed as the mean of three steady-state values: resting (minutes -30, -15, and 0), exercise (minutes 15, 30, and 45), and recovery (minutes 210, 225, and 240).

Statistics. The data was analyzed by using the SPSS (version 11.0). The data are expressed as means ± SE. An independent t-test was used to compare the descriptive data between the GH-deficient and control subjects. A repeated-measures ANOVA was conducted to establish whether there was a difference between the study days (+GH vs. -GH) and the difference over time. A post hoc analysis was conducted if significant main effects were found. A mixed-model ANOVA was used to compare the control group with the +GH day. A P value of <0.05 was considered significant.


   RESULTS
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DISCUSSION
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Subject characteristics are found in Table 2. GH-deficient adults and controls were similar in age and had a similar fat-free mass (FFM), but the GH-deficient subjects were significantly heavier and had a greater body mass index, percent body fat, and fat mass (P < 0.01). The GH-deficient adults were also less fit than the control subjects (P < 0.01). During exercise, the initial power output corresponded to their individual lactate threshold, and the subjects exercised at an identical power output on the +GH and -GH day. As expected during the 45 min of exercise, lactate levels increased significantly over resting levels (P < 0.01) and then returned to resting values during the recovery period (resting, exercise, recovery: +GH: 0.53 ± 0.01, 2.70 ± 0.4, 0.46 ± 0.01; -GH: 0.65 ± 0.01, 2.40 ± 0.5, 0.50 ± 0.00; control: 0.62 ± 0.01, 2.84 ± 0.4, 0.47 ± 0.01 mM, respectively).


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  		Table 2. Physical characteristics and exercise variables for the GH-deficient adults and control subjects

 

Circulating hormones and metabolites. At baseline, there were no differences in the GH levels on the +GH and -GH day (Fig. 1). GH administration was associated with an increase in serum GH concentrations, which reached peak levels (9.77 ± 2.4 µg/l) after 45 min of exercise followed by a rapid decline. The GH administration resulted in a similar pattern of response as was seen in the control group, who also had peak GH concentrations (11.43 ± 3.6 µg/l) at 45 min of exercise. There was no difference between peak GH levels of the +GH day and the control group. GH binding protein levels were similar on both study days in the GH-deficient subjects (resting GH binding protein: +GH 2.1 ± 0.3; -GH 2.2 ± 0.3 nM) and were significantly higher than seen in the control group (1.5 ± 0.2 nM, P < 0.05). No change in the GH binding protein concentrations was observed during exercise and recovery (P = not significant).



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  		Fig. 1. Growth hormone (GH) concentrations at rest, during exercise, and during recovery in the GH-deficient adults with and without GH administered (+GH and -GH, respectively). Values are means ± SE. {dagger}P < 0.01 vs. resting value. {ddagger}P < 0.05, +GH vs. control.

 

Resting insulin and C-peptide concentrations were similar between groups (Table 3). In response to exercise, insulin levels decreased from resting values on both the +GH and -GH day, but the decrease was only significant (P < 0.01) in the control group. During recovery, the insulin levels were lower than resting values in both the GH-deficient and control subjects. Glucagon levels did not change in response to exercise in either the GH-deficient adults or control group. Both epinephrine and norepinephrine concentrations were significantly greater at the end of exercise compared with resting and recovery levels (P < 0.01). These values decreased significantly (P < 0.01) during recovery, and the epinephrine levels were significantly lower (P < 0.01) on the +GH day than on the -GH day. Levels of circulating FFA, alanine, glycerol, and {beta}-hydroxybutyrate are shown in Table 4. In the GH-deficient adults from the resting state to the end of exercise, there was a significant increase (P < 0.05) in plasma concentrations of FFA, alanine, and glycerol, with a decrease during recovery in alanine and glycerol (P < 0.05). {beta}-Hydroxybutyrate concentrations increased slightly during exercise, followed by a significant rise during recovery (P < 0.01); plasma FFA also remained elevated during the recovery period. The control group showed a similar pattern of response in FFA, alanine, glycerol, and {beta}-hydroxybutyrate concentrations as observed on the +GH day. Resting plasma glucose concentrations were 5.3 ± 0.02, 5.0 ± 0.02, and 4.9 ± 0.01 mM for the +GH and -GH day and the control group, respectively, and were stable throughout the study period. No deviations in the glucose levels were found in response to exercise.


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  		Table 3. Insulin, C-peptide, glucagon, and catecholamine levels at rest, the end of exercise, and after 2.5 h of recovery

 

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  		Table 4. FFA, alanine, glycerol, and {beta}-hydroxybutyrate concentrations throughout the study period

 

Whole body metabolism. A significant main effect of time on palmitate flux was found (P < 0.01), as well as a significant treatment effect for study day (+GH vs. -GH, P < 0.01). Post hoc analysis revealed that systemic palmitate flux at rest was similar between the GH-deficient adults with and without GH administration at ~105 µmol/min (Fig. 2). In response to exercise, palmitate flux increased (P < 0.01) to 211 ± 27 and 168 ± 28 µmol/min on the +GH and -GH day, respectively, with the exercise flux on the +GH day being higher than that observed on the -GH day (P < 0.05). Furthermore, during recovery, a subsequent decrease in flux (P < 0.01) was observed on both study days, but the recovery flux remained higher on the +GH day than on the -GH day (P < 0.05). Compared with the control group, there were no differences in the resting or exercise palmitate flux on the +GH day, but during recovery there was a higher flux on the +GH day (P < 0.01). Arterial palmitate concentrations were similar between GH-deficient adults and controls and increased in response to exercise (P < 0.05).



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  		Fig. 2. Palmitate flux at rest, and during exercise and recovery in all subjects. Values are means ± SE. *P < 0.05 vs. GH-deficient adult -GH. {dagger}P < 0.01 vs. resting and recovery values. P < 0.01 vs. recovery concentrations in the control group.

 

Phenylalanine and tyrosine flux were similar between the +GH and -GH conditions at rest and throughout exercise (data not shown). Furthermore, phenylalanine conversion to tyrosine and protein synthesis (phenylalanine disposal not accounted for by phenylalanine conversion to tyrosine) was virtually unchanged throughout the study period. Similarly, on the +GH and -GH day, forearm muscle amino acid Ra showed a trend for higher levels postexercise (t = 60 min; P = 0.06), whereas Rd was significantly increased (P < 0.05), and both Ra and Rd gradually decreased (P < 0.01) back to baseline values during recovery (Fig. 3). However, no significant change in forearm muscle balance was seen at the end of exercise compared with resting values or throughout recovery. Compared with the +GH day, the control group had a similar phenylalanine and tyrosine flux and forearm muscle amino acid Ra and Rd at rest and during recovery from exercise (Fig. 3). There was no change in muscle balance pre- to postexercise in the control group. Forearm blood flow was not found to be significantly different between study days or in the control group and did not change over time in response to exercise (data not shown).



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  		Fig. 3. Muscle protein rate of appearance (A), disappearance (B), and balance (C) throughout the study period. Values are means ± SE. *P < 0.05 vs. preexercise. **P = 0.06 vs. preexercies. {dagger}P < 0.01 over time from time = 50 to postexercise value.

 

Resting metabolic rate, measured by indirect calorimetry, did not change from the morning to afternoon in the controls (morning: 1,782 ± 36; afternoon: 1,733 ± 34 kcal/24 h). In the GH-deficient subjects, no differences were found between study days. The afternoon resting metabolic rate value was greater than the morning resting metabolic rate value on the +GH day, but this was not statistically significant (+GH: 1,897 ± 72 vs. 1,937 ± 117; -GH: 1,751 ± 77 vs. 1,754 ± 125 kcal/24 h, respectively). There was a trend for a decrease in the RER on both study days in the GH-deficient subjects from the morning to afternoon measurement (+GH: 0.82 ± 0.02, 0.80 ± 0.02; -GH: 0.88 ± 0.02, 0.82 ± 0.02 kcal/24 h, respectively; P < 0.06). The control subjects showed a significant decrease in RER values from morning to afternoon (0.87 ± 0.01 vs. 0.79 ± 0.02 kcal/24 h, respectively; P < 0.01).

Glucose turnover was not different between the +GH and -GH study day before exercise (Fig. 4). A significant time effect was found in glucose turnover (P < 0.01) throughout the study period, with a significant increase during exercise and a return to resting values throughout the recovery period. Glucose Rd was not different between study days. Likewise, the control group displayed a higher (P < 0.05) Ra postexercise, and this increase was greater than that seen on the -GH day (P < 0.05). There were no differences in the Rd between the control group and the +GH day.



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  		Fig. 4. Glucose rate of appearance (A) and disappearance (B) throughout the study period. Values are means ± SE. *P < 0.05 controls vs. -GH condition at the end of exercise. {dagger}P < 0.01 for time effect.

 


   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
The present study is, to our knowledge, the first to assess the impact of acute GH administration on lipid metabolism in human subjects. The inclusion of GH-deficient adults in addition to a control group of healthy subjects provided an experimental model to closely imitate a physiological GH bolus as well as to study the effects of GH withdrawal. Systemic palmitate flux, phenylalanine and tyrosine flux, and glucose Ra and Rd were measured at exercise levels known to result in moderate stimulation of metabolism. The primary findings for this study were 1) restoration of GH levels in GH-deficient individuals during exercise stimulates FFA release and turnover, and 2) acute GH administration does not significantly impact glucose or protein metabolism during exercise.

The success of studying GH function during exercise was dependent on our ability to mimic the pattern of GH release typically seen in healthy individuals. We were able to obtain a very similar pattern of GH release on the +GH day as is seen in the control subjects, which was similar to data from the literature (15, 30). Regardless of the study day, comparable hormonal changes during exercise, in terms of insulin, glucagon, catecholamines, and GH levels, were observed with each hormone and changed in a manner expected to stimulate lipolysis. At rest, no differences in FFA flux with or without GH were observed, which was unlike previous studies where GH administration had important lipolytic properties at rest (2, 6). In response to exercise, there was a dramatic increase in the systemic FFA flux on both the +GH and -GH day, which was ~75-100% higher than resting values. Administration of GH, however, resulted in the FFA flux being ~20% higher on the +GH day compared with the -GH day.

It is evident from the present and previous studies that increases in epinephrine and norepinephrine, as well as a decrease in insulin concentrations, promote lipolysis during exercise (33). It has been suggested that GH may have an indirect effect on lipolysis via stimulation of the {beta}-adrenergic receptor (1). Furthermore, if the activity of GH on adipose tissue is predominantly indirect, GH may have a more delayed effect on the FFA release from the adipose tissue (3), which may have a more profound impact during longer duration exercise, or during recovery as we observed in the present study. Møller et al. (24) observed that the greatest lipolytic effects from a GH infusion administered at rest were ~120 min after the infusion was initiated. On the +GH day, we found that the palmitate flux during recovery was ~27% higher than on the -GH study day. Because we do not have indirect calorimetry data during or immediately after exercise, we were unable to establish whether FFA oxidation was also enhanced during this period, although a lower RER value was found in the afternoon on the +GH day compared with the -GH day.

Very little research is available concerning the effect of GH administration during exercise. Lange et al. (17) noted that in healthy subjects a greater rise in plasma glycerol and nonesterified fatty acid concentrations occurred during exercise when a supraphysiological dose of GH was injected subcutaneously 4 h prior. Discontinuation of GH substitution for 3 mo in GH-deficient adults has been shown to result in reductions in glycerol and FFA release into the circulation both at rest and during moderately intense exercise (10). Our study was unique because the GH was administered in a manner that mimicked the normal GH release typically seen in a healthy individual. Our findings extend the present knowledge by indicating that, in GH-deficient men who chronically received GH, administration of GH during exercise can acutely stimulate lipolysis; furthermore, this can be accomplished at doses of GH that mimic the response seen in healthy men.

Previous literature shows that exercise results in either no change (29) or only slight increases (4) in whole body protein synthesis rates in response to prolonged exercise at 40 or 65% O2 peak. In the present study, immediately after the exercise period (t = 60 min), there was a 1.5- to 2-fold increase in the muscle Ra and Rd over the preexercise levels (t = -15 min; Fig. 3) and then a decline back to resting values. Therefore, overall, there was no change in muscle protein balance. Our findings are consistent with these earlier reports, and because our subjects only exercised for 45 min at a moderate intensity, the exercise duration may have been too short to see a significant impact on protein metabolism. Previous studies assessing the impact of GH on protein metabolism at the whole body level have shown that acute exposure to high levels of GH increases protein synthesis (9, 31). In contrast, our findings demonstrate that, despite physiologically high GH concentrations with GH treatment, there were no differences in protein synthesis compared with the -GH day. This finding contrasts the aforementioned studies (9, 31) but is in agreement with others that observed no stimulation of muscle protein synthesis despite enhanced protein synthesis in nonmuscle tissue after a 3.5-h infusion of GH (6). In addition, despite an exercise-induced increase of lipid substrates (FFA or {beta}-hydroxybutyrate), there did not appear to be any systemic protein-conserving effects. Possibly, if leg balance was measured, there may have been different local effects on protein synthesis, because this was cycle ergometer exercise

Resting and exercise glucose Ra were similar on both study days and in the control group. Both the GH-deficient and control subjects had a decrease in Ra during recovery; however, the recovery Ra values were greater in the controls than seen on the +GH day. The increased Ra was paralleled by an increased Rd at the end of exercise, resulting in no differences in the plasma glucose concentrations. This suggests a close matching of glucose release with uptake not only in working muscles but also systemically. GH replacement back to GH-deficient adults who chronically receive GH had no effect on glucose levels, supporting earlier work showing that short-term GH administration does not influence glucose metabolism in the basal state (23). In contrast, GH is found to inhibit peripheral glucose clearance after 2-3 h during hyperinsulinemic euglycemic clamps (22), indicating that GH inhibition of muscle glucose uptake plays a quantitatively far more important role during hyperinsulinemia. During exercise, insulin levels actually decrease because of the simultaneous muscle contraction-stimulated glucose uptake, so the impact of GH on glucose turnover may have been attenuated.

In summary, we tested the effects of acute GH administration on lipid, protein, and glucose metabolism during moderate-intensity exercise in GH-deficient adults. Administration of GH increased lipolysis during and immediately after exercise to levels similar to healthy subjects, which supports the argument that the primary effect of GH is to augment the release and utilization of fatty acids. Although lipid metabolism was altered by GH administration in the GH-deficient adults, it had no impact on glucose or protein metabolism.


   GRANTS
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 ABSTRACT
 METHODS
 RESULTS
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REFERENCES
 
This project was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-40484.


   FOOTNOTES
 

Address for reprint requests and other correspondence: J. A. Kanaley, 820 Comstock Ave., Rm. 201, Syracuse, NY 13244 (E-mail: jakanale{at}syr.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
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  1. Beauville M, Harnat I, Crampes F, Riviere D, Tauber MT, Tauber JP, and Garrigues M. Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response. Am J Physiol Endocrinol Metab 263: E467-E472, 1992.[Abstract/Free Full Text]
  2. Boyle PJ, Avogaro A, Smith L, Bier DM, Pappu AS, Illingworth DR, and Cryer PE. Role of GH in regulating nocturnal rates of lipolysis and plasma mevalonate levels in normal and diabetic humans. Am J Physiol Endocrinol Metab 263: E168-E172, 1992.[Abstract/Free Full Text]
  3. Brooks GA, TDFAhey White TP, and Baldwin KM. Exercise Physiology: Human Bioenergetics and Its Applications. Mountain View, CA: Mayfield Publishing, 1999.
  4. Carraro F, Stuart CA, Hartl WH, Rosenblatt J, and Wolfe RR. Effect of exercise and recovery on muscle protein synthesis in human subjects. Am J Physiol Endocrinol Metab 259: E470-E476, 1990.[Abstract/Free Full Text]
  5. Chalmers RJ, Bloom SR, Duncan G, Johnson RH, and Sulaiman WR. The effect of somatostatin on metabolic and hormonal changes during and after exercise. Clin Endocrinol (Oxf) 10: 451-458, 1979.[Medline]
  6. Copeland KC and Nair KS. Acute growth hormone effects on amino acid and lipid metabolism. J Clin Endocrinol Metab 78: 1040-1047, 1994.[Abstract]
  7. Erikkson BM and Persson AB. Determination of catecholamines in rat heart tissue and plasma samples by liquid chromatography. J Chromatogr B Biomed Appl 228: 143-154, 1982.[CrossRef]
  8. Fryburg DA and Barrett EJ. Growth hormone acutely stimulates skeletal muscle but not whole-body protein synthesis in humans. Metabolism 42: 1223-12277, 1993.[CrossRef][ISI][Medline]
  9. Fryburg DA, Gelfand RA, and Barrett EJ. Growth hormone acutely stimulates forearm muscle protein synthesis in normal humans. Am J Physiol Endocrinol Metab 260: E499-E504, 1991.[Abstract/Free Full Text]
  10. Gibney J, Healy ML, Stolinski M, Bowes SB, Pentecost C, Breen L, McMillan C, Russell-Jones DL, Sonksen PH, and Umpleby AM. Effect of growth hormone (GH) on glycerol and free fatty acid metabolism during exhaustive exercise in GH-deficient adults. J Clin Endocrinol Metab 88: 1792-1797, 2003.[Abstract/Free Full Text]
  11. Hirsch IB, Marker JC, Smith LJ, Spina RJ, Parvin CA, Holloszy JO, and Cryer PE. Insulin and glucagon in prevention of hypoglycemia during exercise in humans. Am J Physiol Endocrinol Metab 260: E695-E704, 1991.[Abstract/Free Full Text]
  12. Jensen MD, Haymond MW, Gerich JE, Cryer PE, and Miles JM. Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. J Clin Invest 79: 207-213, 1987.[ISI][Medline]
  13. Johnson RH, Rennie MJ, Walton JL, and Webster MH. The effect of moderate exercise on blood metabolites in patients with hypopituitarism. Clin Sci (Colch) 40: 127-136, 1971.
  14. Jones B and Gilligan J. Amino acid analysis by O-pthaldehyde precolumn derivitization and reversed phase HPLC. Am Biotechnol Lab 12: 45-51, 1983.
  15. Kanaley JA, Weltman JY, Pieper KS, Weltman A, and Hartman ML. Cortisol and growth hormone responses to exercise at different times of day. J Clin Endocrinol Metab 86: 2881-2889, 2001.[Abstract/Free Full Text]
  16. Kanaley JA, Weltman JY, Veldhuis JD, Rogol AD, Hartman ML, and Weltman A. Human growth hormone response to repeated bouts of aerobic exercise. J Appl Physiol 83: 1756-1761, 1997.[Abstract/Free Full Text]
  17. Lange KH, Larsson B, Flyvbjerg A, Dall R, Bennekou M, Rasmussen MH, Orskov H, and Kjaer M. Acute growth hormone administration causes exaggerated increases in plasma lactate and glycerol during moderate to high intensity bicycling in trained young men. J Clin Endocrinol Metab 87: 4966-4975, 2002.[Abstract/Free Full Text]
  18. Lucidi P, Parlanti N, Piccioni F, Santeusanio F, and De Feo P. Short-term treatment with low doses of recombinant human GH stimulates lipolysis in visceral obese men. J Clin Endocrinol Metab 87: 3105-3109, 2002.[Abstract/Free Full Text]
  19. Marker JC, Hirsch IB, Smith LJ, Parvin CA, Holloszy JO, and Cryer PE. Catecholamines in prevention of hypoglycemia during exercise in humans. Am J Physiol Endocrinol Metab 260: E705-E712, 1991.[Abstract/Free Full Text]
  20. McArdle WD, Katch FI, and Katch VL. Exercise Physiology: Energy, Nutrition, and Human Performance. Philadelphia, PA: Williams & Wilkins, 2001.
  21. Miles JM, Ellman MG, McClean KL, and Jensen MD. Validation of a new method for determination of free fatty acid turnover. Am J Physiol Endocrinol Metab 252: E431-E438, 1987.[Abstract/Free Full Text]
  22. Møller N, Butler PC, Antsiferov M, and Alberti KGMM. Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man. Diabetologia 32: 105-110, 1989.[CrossRef][ISI][Medline]
  23. Møller N, Jørgensen JOL, Alberti KGMM, Flyvbjerg A, and Schmitz O. Short-term effects of growth hormone on fuel oxidation and regional substrate metabolism in normal man. J Clin Endocrinol Metab 70: 1179-1186, 1990.[Abstract]
  24. Møller N, Jørgensen JOL, Schmitz O, Møller J, Christiansen J, Alberti KGMM, and Ørskov H. Effects of a growth hormone pulse on total and forearm substrate fluxes in humans. Am J Physiol Endocrinol Metab 258: E86-E91, 1990.[Abstract/Free Full Text]
  25. Møller N, Porksen N, Ovesen P, and Alberti KGMM. Evidence for increased sensitivity of fuel mobilization to growth hormone during short-term fasting in humans. Horm Metab Res 25: 175-179, 1993.[ISI][Medline]
  26. Nair KS, Ford GC, Ekberg K, Fernqvist Forbes E, and Wahren J. Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients. J Clin Invest 95: 2926-2937, 1995.[ISI][Medline]
  27. Nørrelund H, Nair KS, Jørgensen JOL, Christiansen JS, and Møller N. The protein-retaining effects of growth hormone during fasting involve inhibition of muscle-protein breakdown. Diabetes 50: 96-104, 2001.[Abstract/Free Full Text]
  28. Øskov H, Thomsen HG, and Yde H. Wick chromatography for rapid and reliable immunosassay of insulin, glucagon and growth hormone. Nature 219: 193-195, 1968.[Medline]
  29. Phillips SM, Atkinson SA, Tarnopolsky MA, and MacDougall JD. Gender differences in leucine kinetics and nitrogen balance in endurance athletes. J Appl Physiol 75: 2134-2141, 1993.[Abstract/Free Full Text]
  30. Pritzlaff CJ, Wideman L, Weltman JY, Abbott RD, Gutgesell ME, Hartman ML, Veldhuis JD, and Weltman A. Impact of acute exercise intensity on pulsatile growth hormone release in men. J Appl Physiol 87: 498-504, 1999.[Abstract/Free Full Text]
  31. Russell-Jones DL, Weissberger AJ, Bowes SB, Kelly JM, Thomason M, Umpleby AM, Jones RH, and Sonksen PH. The effects of growth hormone on protein metabolism in adult growth hormone deficient patients. Clin Endocrinol (Oxf) 38: 427-431, 1993.[Medline]
  32. Thompson GN, Pacy PJ, Merritt H, Ford GC, Read MA, Cheng KN, and Halliday D. Rapid measurement of whole body and forearm protein turnover using a [3H3] phenylaline model. Am J Physiol Endocrinol Metab 256: E631-E639, 1989.[Abstract/Free Full Text]
  33. Wasserman DH, Lacy DB, Goldstein RE, Williams PE, and Cherrington AD. Exercise-induced fall in insulin and increase in fat metabolism during prolonged muscular work. Diabetes 38: 484-490, 1989.[Abstract]
  34. Whitney RJ. The measurement of volume-change in human limbs. J Physiol 121: 1-27, 1953.[Free Full Text]



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