Metabolic Unit, 1 Service Central de Physiologie Clinique: Centre d'Exploration et de Réadaptation des Anomalies Métaboliques et Musculaires, and 2 Service de Médecine Nucléaire, hôpital Lapeyronie, 34295 Montpellier; and 3 Service de Biochimie B, Centre Hospitalier Universitaire, Saint Eloi, 34295 Montpellier, France
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ABSTRACT |
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The aim of this study was to
compare circulating levels of growth hormone (GH), IGF-I, and
IGF-binding protein (IGFBP)-1 and IGFBP-3 in response to a
long-duration endurance exercise in trained vs. sedentary middle-aged
males and to determine whether a relationship with glucose homeostasis
exists. Seven trained men (Tr) were compared with seven age-matched
sedentary men (Sed) during two trials of 60 min of cycling exercise
performed below (VT) and above (+VT) the ventilatory threshold.
Insulin sensitivity (SI) was higher in Tr than in Sed
(P < 0.001). Basal GH, IGF-I, and IGFBP-1 and -3 were
higher in Tr (P < 0.05). During +VT, Tr had a
threefold higher GH response, whereas their blood glucose level was
better maintained (P < 0.05). Basal IGFBP-1 was
correlated with SI (P < 0.01). These data
indicate that endurance training in middle-aged men increased the
activity of the GH/IGF-I system and improved glucoregulation both at
rest and during high-intensity endurance exercise.
endurance training; insulin sensitivity; insulin-like growth factor I; insulin-like growth factor-binding protein-1 and -3; middle age
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INTRODUCTION |
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HIGH LEVELS OF ACTIVITY AND FITNESS have been shown to increase both the secretion of the growth hormone/insulin-like growth factor I (GH/IGF-I) axis (10, 14) and glucose disposal (17, 26, 27). Furthermore, the decline in GH secretion (22, 29, 32), plasma IGF-I (22, 32, 33, 34), and insulin sensitivity (SI) (11, 12) that occur with aging may be related in part to a decline in physical fitness. This process is particularly relevant for middle-aged individuals, because the insulin resistance (11, 12) and progressive reduction in the GH secretion rate (16, 39) of aging are initiated as early as the third decade of life. It has recently been shown that low plasma IGF-I concentrations are predictive of a decline in whole body glucose uptake in older people (9). Although it is well documented that circulating levels of IGF-I are regulated by insulin and GH, evidence is accumulating that exercise is potentially another important regulator of IGF-I levels (21). Thus these age-related declines in anabolic hormone status (9, 34) and glucose disposal (17, 26) may both be restored by training. However, most IGF-I circulates in blood bound to a family of IGF-binding proteins (designated IGFBP-1 to -6), which have been shown to modulate IGF-I availability for action on tissues (36). IGFBP-1 and IGFBP-3 are considered to be the best characterized of the six circulating IGFBPs (31), but the evidence is conflicting regarding the effects of regularly performed exercise on IGFBP levels. One study found no effect of exercise on IGFBP-1 and -3 in the elderly (34), whereas another observed increased IGFBP-1 levels in middle-aged men (18). An involvement of IGF-I and its binding protein IGFBP-1 in glucose homeostasis has been proposed, because alterations in IGF-I availability may modulate its insulin-like effects (19, 23, 37). In addition, constitutive overexpression of IGFBP-1 results in impaired glucose tolerance with normal SI (35). There is a paucity of data on the interaction of prolonged exercise, especially at different intensities, and both carbohydrate homeostasis and the GH/IGF-I axis responses. All of the studies considered, however, were performed with elderly subjects (between 60 and 70 yr of age), although, as mentioned above, the critical period for a progressive reduction in both the GH secretion rate and SI is during early middle age (11, 12, 16, 39); almost nothing seems to be known in the middle-aged population. Our working hypothesis in this study was, therefore, that training would induce important alterations of both glucoregulation and GH/IGF-I axis in middle-aged subjects and that these two mechanisms are related to each other. Therefore, this study was undertaken to investigate in middle-aged subjects 1) to what extent and at which intensity level (below or above VT or both) training modifies plasma GH, IGF-I, and IGFBP-1 and -3 and 2) whether a relationship to glucose homeostasis exists, especially regarding glucoregulation adaptation to a long-duration exercise.
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METHODS |
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Subjects.
Seven middle-aged endurance-trained cyclists (Tr) and seven middle-aged
sedentary men (Sed) participated in this study. None had a family
history of diabetes or hypertension. Smokers or those currently using
medication for the control of blood arterial pressure and lipid or
carbohydrate metabolism were excluded. No subject exhibited
electrocardiogram abnormalities at rest or during a maximal cycle
ergometer test. The physical characteristics of the subjects are shown
in Table 1. Body composition was assessed with a four-terminal impedance plethysmograph, the Dietosystem Human
IM-Scan (25). The training program for the cyclists was a
collective activity, as all were members of the same cycling club. They
cycled almost 10 h/wk (300 ± 15 km) and had been doing so for
10 ± 1.5 yr.
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Protocol.
The subjects came to the laboratory on four separate days for
1) the glucose tolerance test (day 1),
2) an incremental maximal exercise test for the
determination of the maximal oxygen uptake (O2 max) and ventilatory threshold (VT)
(day 2), and 3) two 60-min steady-state exercise
tests, one below (
15%) and the other above (+15%) their individual
VT. These tests were performed in random order (days 3 and 4).
Insulin action. An intravenous glucose tolerance test was performed according to the minimal model of Bergman et al. (2) with TISPAG software from the Department of Physiology, University of Montpellier I (7), which uses a nonlinear least squares estimation. Subjects were asked to fast for 12 h before the test, which began at 9 AM. A cannula was inserted in the cephalic vein at the level of the cubital fossa for blood sampling at various times, and a glucose injection was administered via the contralateral cephalic vein. Glucose (0.5 g/kg, solution at 30%) was slowly injected over 3 min. Insulin (0.02 U/kg body wt; i.e., 1-2 U) was immediately injected intravenously at 19 min. Blood samples were drawn twice before the glucose bolus and at 1, 3, 4, 8, 10, 15, 19, 20, 22, 30, 41, 70, 90, and 180 min after the end of glucose injection.
Measurement of SI.
The minimal model is a mathematical analysis of the frequently sampled
intravenous glucose tolerance test (2). This program gave
the value of SI, which is a measure of the dose-response relationship between plasma insulin and glucose disposal. It gave the
values of SI from the following equations
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Incremental maximal exercise test.
The subject's maximal oxygen consumption
(O2 max) was measured during 8-12
min of exercise on an electronically braked cycle ergometer (550 ERG,
Bosch, Berlin, Germany). Fractions of oxygen and carbon dioxide in the
expired air were measured by a mass spectrometer (Marquette MGA 1100, St. Quentin, France). The calibration of the mass spectrometer
was checked before each test with standard calibration gases. A 3-l
syringe was used to calibrate the volume turbine by use of flow rates
similar to subject ventilation. Heart rates were monitored throughout
the exercise test. Exercise testing started with a 3-min warm-up at 40 W. The workload was increased by steps of 20 W for the sedentary group and 30 W for the trained group every minute until maximal exercise was
reached. This was evaluated in terms of maximal heart rate, respiratory
exchange ratio (RER) values (>1.15), and O2 consumption (
O2) stability. The estimation of the
ventilatory threshold (VT) was performed by analysis of the behavior of
carbon dioxide production (
CO2) vs.
O2 following the V-slope according to the method of Beaver et al. (1).
Steady-state exercise tests.
Subjects arrived at the laboratory at 8 AM after an overnight fast
(i.e., 12 h). A Teflon catheter was inserted in the cephalic vein
at the level of the cubital fossa for blood sampling at various times.
At 8:30 AM, a resting blood sample was drawn for subsequent analysis,
and subjects then exercised either below (15%) or above (+15%)
their VT for 60 min on an electronically braked cycle ergometer (550 ERG). During the 60 min of exercise, the subjects were instructed to
maintain a pedaling rate of 75 rpm. Ventilation
(
E), RER,
O2, and
CO2 were measured continuously, as
described in the preceding section. During this period,
O2 and
CO2 varied by <0.1 l/min, and
E varied by <0.5 l/min.
Sample collection and analysis.
Blood samples were drawn at rest (time 0) and at 5, 15, 30, 45, and 60 min during exercise. The samples were immediately placed in
a tube containing lithium heparin (glucose, insulin, GH, IGF-I, and
IGFBP-1 and -3) or EDTA (lactate). The plasma was immediately separated
by centrifugation at 4°C and was stored at 80°C until analysis.
Statistical analysis. A Student's t-test was used to compare the physical characteristics and SI between the two groups. The significance of differences between the Tr and Sed groups during moderate and hard exercise intensity was determined using a two-way analysis of variance (ANOVA). To assess the patterns of response in the groups, plasma substrates and/or hormone concentrations were compared by ANOVA with repeated measures. To evaluate the relationship between SI and basal hormonal responses, Spearman's rank order analysis was performed. Significance was defined as P < 0.05. Data are presented separately as means ± SE.
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RESULTS |
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Physical characteristics, ergometric parameters, and
O2 measurement.
The Sed and Tr groups did not differ with respect to age,
height, weight, body fat, body mass index (BMI), or VT. However,
O2 max, maximal power
(Wmax), and power at VT (W/VT) were higher in Tr than in
Sed (P < 0.001). When intensity during the two
sessions (
VT and +VT) was expressed as a percentage of
O2 max, these percentages were quite
similar for Tr and Sed: respectively, 50.1 ± 2.2 vs. 51.2 ± 3.1% below VT and 71.2 ± 1.6 vs. 73.6 ± 2.4% above VT.
SI.
Fasting values of plasma glucose and plasma insulin were lower in Tr
than in Sed (0.84 ± 0.01 vs. 0.90 ± 0.02 g/l and 6.85 ± 0.7 vs. 10.5 ± 1.36 µU/ml, P < 0.03).
Compared with Sed, Tr had higher SI {15.2 ± 3.1 vs.
2.99 ± 0.6 [×104(µU · ml
1 · min
1)],
P < 0.001}.
Substrate concentrations and plasma hormones at rest and during
exercise.
Hematocrit values were not significantly different during exercise
tests. Although baseline plasma glucose concentrations were not
different between Tr and Sed, glucose concentrations were higher at 30, 45, and 60 min in Tr when exercise was performed above VT
(P < 0.05; Fig. 1).
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Correlation studies.
Basal IGFBP-1 was correlated with SI in Tr
(r = 0.75, P < 0.03). Basal IGF-I was
correlated with Wmax in Tr (r = 0.84, P < 0.01). When we grouped all the
middle-aged men together, basal IGFBP-3 was positively correlated with
O2 max (r = 0.55, P < 0.05), and SI was correlated
positively with basal IGFBP-1 and negatively with the percentage of
fatness (respectively, r = 0.89, P < 0.01 and r =
0.91, P < 0.01; Fig.
3). Basal IGFBP-1 was not significantly
correlated with the percentage of fatness (r = 0.29, P = 0.28).
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DISCUSSION |
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This study was undertaken to investigate the effects of training at middle age on both the GH/IGF-I axis and glucose homeostasis (both at rest and during prolonged exercise) and to look for possible relationships between these two functions. Results show that middle-aged trained subjects have increased baseline levels of plasma GH, IGFBP-1, IGFBP-3, and IGF-I. Both IGFBP-3 and IGF-I exihibit correlations with aerobic working capacity. GH response during prolonged exercise either below or above VT is higher in trained compared with sedentary subjects. On the other hand, SI is higher in trained subjects and is correlated positively with IGFBP-1 and negatively with fat mass.
This study was designed as a cross-sectional comparison of carefully matched subjects. It is clear that an effect of training would have been demonstrated with more statistical strength with a longitudinal study. Therefore, we tried hard to control for all of the possible confusion factors such as body composition, age, weight, height, gender, nutritional status, pattern of physical activity, GH and IGF status, and glucoregulation. Concerning our trained population, training was performed in the same cycling team, and subjects exercised together, were given the same diet guidelines, and performed at exactly the same intensity and volume of exercise. Our sedentary controls were carefully matched with these trained subjects with regard to age, gender, BMI, and percentage of fat mass, i.e., all major factors of confusion for the parameters investigated in this experiment. Thus our results very likely reflect mainly the effect of training.
Another methodological aspect of this study that needs comment is the exercise protocol. We chose 60-min steady-state exercise, i.e., a situation where blood glucose levels need to be maintained by regulation of hormonal mechanisms whose failure may result in hypoglycemia. There was a paucity of studies related to this kind of exercise, especially at middle age. In particular, we were not aware of reports of prolonged exercise above VT in sedentary middle-aged individuals. Although they found this quite difficult, our untrained subjects were able to complete this protocol and thus provide us a picture of what occurs in this condition.
The effects of exercise and training on IGF-I and its binding proteins IGFBP-1 and -3 remain incompletely understood, more especially at the critical period that is middle age, when GH and IGF-I decline (16, 39). Several authors, however, have described an increase in plasma IGF-I after endurance training (21, 34), whereas others have reported an opposite effect (14, 15). Moreover, exercise and training have been reported to increase IGFBP-1 (18, 30) and IGFBP-3 (21, 30), but there is not general agreement about this finding (13). The discrepancies among these studies are likely to be explained in great part by differences in either subject training level, body composition status, or age. The literature contains few studies at any exercise intensity, particularly on middle-aged subjects and the possible involvement of these factors in exercise-induced modifications in glucose disposal. To our knowledge, ours is the first study to investigate GH, IGF-I, and IGFBP-1 and -3 during prolonged exercise at both moderate and high intensities in relation to glucose homeostasis in middle-aged trained and sedentary men.
One of the main determinants of the magnitude of GH response to
endurance-type exercise is the intensity of exercise (10). Thus GH response increases progressively during exercise up to 100%
O2 max (29). Aging,
however, decreases GH levels (22, 28, 32) after 40 yr of
age (16, 39). The present study shows that, during
exercise, the rise in plasma GH was almost threefold higher in the
middle-aged trained men than in the sedentary men at both intensities.
We can explain this result by the positive effect of physical fitness
on GH response during exercise (10). It is interesting to
point out that, as can be clearly observed in Fig. 2, prolonged
exercise induces a sustained GH response both below and above VT in the
group of trained subjects, resulting in a large amount of GH
physiologically delivered in blood. These levels of GH are similar to
those observed after exercise in 20-yr-old subjects. Because they are
associated with higher resting values of IGF-I and IGFBP-3, they can be
assumed to exert an anabolic effect. It is interesting to notice, as
shown in Fig. 2, that no clear difference can be detected between GH
responses below and above VT, consistent with a previous report
(24) that indicated that, above 75%
O2 max, GH response to exercise no
longer increased. Therefore, a long-duration exercise session 15%
below the VT appears to be sufficient to achieve, in trained subjects, this large and sustained GH response, whereas exercising above this
level does not appear to markedly improve this response.
On the whole, therefore, it appears obvious that training is responsible for an increase in secretory activity of the GH/IGF-I axis in middle-aged men. This increase is reflected by higher GH response but also by higher baseline values of IGF-I and IGFBP-3. The levels of these two proteins remain unchanged during exercise. All this suggests that the age-associated decline in somatotropic system activity (28, 32) may be attenuated by endurance training. In accord with this finding, Poehlman et al. (34) concluded that endurance training increases the fasting level of IGF-I in older individuals. However, a recent study did not support this finding and showed that only IGFBP-1 was higher in marathon runners than in age-matched sedentary controls (13). One explanation for this finding may be the significant difference in BMI between groups. Thus the low body fat percentage in these runners may have modified the GH/IGF-I response (8). In the present study, we matched subjects for body composition (i.e., BMI and percentage of fatness) to avoid the impact of this parameter. Another explanation could be the specific interactions of duration and intensity during different types of endurance exercise (e.g., running vs. cycling).
In the present study, we found a correlation between basal IGFBP-3 and
O2 max, as prevously described in young
subjects (4, 5). Because IGFBP-3 is considered to be an
integrated index of GH action (3), this increase is likely
to reflect the training-induced amplification of the secretory activity
of the GH/IGF axis that has been previously reported (10).
In view of these remarks, we suggest that IGFBP-3 is an endocrine
marker of physical fitness. Two other studies (22,
34) have demonstrated a positive relationship between IGF-I and
O2 max. Poehlman et al.
(34), however, showed that this association is less robust in older men. The authors explained this, in part, by a tendency toward
less frequent and less intense exercise in older men, which may explain
why our correlation between IGF-I and Wmax was found only
in the middle-aged trained individuals.
This study evidenced several effects of training on glucose tolerance mechanisms. First, trained subjects at both ages have a markedly increased SI. This finding is consistent with previous reports (26, 27) and shows that regular exercise is able to counteract the decline in SI that occurs at this age. Because insulin resistance is a major factor involved in the development of metabolic and circulating disturbances that occur at this age (11, 12), the strong beneficial effect of training on this parameter may contribute to an explanation of the recently demonstrated efficiency of regular exercise in the prevention of type 2 diabetes (38). Training appears also to be associated with alterations in the glucoregulation adaptation to exercise. As shown in Fig. 1, trained subjects exhibit both a better stability of blood glucose during prolonged exercise and a significant decrease of insulinemia when cycling above VT. This response indicates a metabolic adaptation to prolonged exercise that may to some extent prevent the decline in blood glucose that occurs during prolonged exercise and is assumed to induce fatigue and decreased performance. Such long-duration exercise sessions at high-power intensity (above VT) are relevant to some usual situations in middle-aged subjects, e.g., intense and prolonged leisure cycling sessions. Thus it is interesting to notice that trained subjects exhibit a metabolic adaptation that seems to be worthwhile for coping with this situation. However, the mechanism for this effect of training is not fully explained by the information collected in this study.
One could suggest a first explanation related to the absolute power
output. Although the trained men worked at the same relative intensity
(i.e., 70% of O2 max), they had a
higher absolute intensity. However, the difference between groups was
not important (+50 W below VT and +70 W above VT). Theoretically,
catecholamines may be involved in this mechanism, more especially above
VT. In fact, the trained men had a higher Epi response than the
sedentary men at the end of exercise performed above VT, but there was
also no clear workload-related difference in catecholamine response and
glycemia. Moreover, there was no positive correlation between catecholamines and blood glucose, but rather a negative one (between Epi and blood glucose), which is likely to reflect more the effect of
these hormones on glycolysis than their hyperglycemic action. Thus neither differences in absolute workload nor differences in
catecholamine responses appear to provide a satisfactory explanation for differences between trained and sedentary men.
The GH/IGF-I axis can also be hypothesized to play a role in this specific pattern observed in the trained men, keeping in mind that in these subjects it has also undergone very marked modifications. There is clearly a link in this study between the GH/IGF-I axis and glucoregulation, as shown in Fig. 3, with the positive correlation between SI and IGFBP-1. It is assumed to reflect a homeostatic loop aimed at preventing hypoglycemia in subjects whose SI is high and in whom IGF-I may thus result in hypoglycemia. A more specific role of IGFBP-1 as a factor preventing hypoglycemia at exercise has also been suggested (19, 30). Although in our study the trained men had both a higher IGFBP-1 concentration in blood and a better stability of glucose at exercise, there is no obvious relationship between these two phenomena, and we do not provide additional evidence for this so-called "antihypoglycemic role of IGFBP-1" (19, 30).
In summary, the present study shows that training increases both the
secretory activity of the somatotrope axis (GH/IGF-I) and
SI in middle-aged men. These findings further support the notion that age-related declines in activity of the GH/IGF-I axis and
glucose tolerance in middle-aged men can be improved by endurance training. During 1-h endurance sessions, both below and above VT, there
is a sustained GH response, which is markedly amplified in trained men.
In addition, basal IGFBP-3 was correlated with O2 max, as previously reported in young
subjects (4, 5), further suggesting IGFBP-3 as an
endocrine marker of physical fitness. On the other hand, basal IGFBP-1
is higher in trained men and is correlated with SI.
Finally, training is also associated with a stronger insulin decrease
and a lack of decrease in blood glucose during high-intensity exercise.
Therefore, endurance training in middle-aged men induced several
metabolic and hormonal alterations that are associated with an
improvement in glucose homeostasis at rest and during exercise and with
an increased activity of the GH/IGF-I axis. However, the causal
relationships among all these modifications remain unclear and will
require additional studies.
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ACKNOWLEDGEMENTS |
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We thank the laboratory of Pr. C. Sultan and Dr. S. Lumbroso (Service d'Endocrinologie de la Reproduction, CHU Lapeyronie) for the radioimmunoassays, and Novo Nordisk France for financial support.
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FOOTNOTES |
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Address for reprint requests and other correspondence: J. Manetta, Service Central de Physiologie Clinique (CERAMM), Hôpital lapeyronie, 371 Ave. du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France (E-mail: jerome.manetta{at}free.fr).
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.
June 25, 2002;10.1152/ajpendo.00539.2001
Received 5 December 2001; accepted in final form 18 June 2002.
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REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Beaver, WL,
Wassermann K,
and
Whipp BJ.
A new method for detecting anaerobic threshold by gas exchange.
J Appl Physiol
60:
217-225,
1986.
2.
Bergman, RN,
Ider YZ,
Bowden CR,
and
Cobelli C.
Quantitative estimation of insulin sensitivity.
Am J Physiol Endocrinol Metab Gastrointest Physiol
236:
E667-E677,
1979
3.
Blum, WF,
Albertsson-Wikland K,
Rosberg S,
and
Ranke MB.
Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion.
J Clin Endocrinol Metab
76:
1610-1616,
1993[Abstract].
4.
Brun, JF,
Blanchon C,
Micallef JP,
Fédou C,
Charpiat A,
Bouix O,
and
Orsetti A.
Serum insulin-like growth factor-binding protein concentrations in highly trained adolescent gymnasts.
Sci Sports
11:
157-165,
1996.
5.
Brun, JF,
Dieu-Cambrézy C,
Charpiat A,
Fons C,
Fédou C,
Micallef JP,
Fusselier M,
Bardet C,
and
Orsetti A.
Serum zinc in highly trained adolescent gymnasts.
Biol Trace Elem Res
47:
273-278,
1995[ISI][Medline].
6.
Brun, JF,
Fédou C,
Monnier JF,
Jourdan N,
and
Orsetti A.
Relationships between insulin resistance measured with the minimal model and microalbuminuria in type 2 (non-insulin dependent) diabetics.
Endocrinol and Metab
2:
203-2135,
1995.
7.
Brun, JF,
Guintrand-Hugret R,
Boegner R,
Bouix O,
and
Orsetti A.
Influence of short submaximal exercise on parameters of glucose assimilation analyzed with the minimal model.
Metabolism
44:
833-840,
1995[ISI][Medline].
8.
Copeland, KC,
Coletti RB,
Devlin JT,
and
McAuliffe TL.
The relationship between insulin-like growth factor-1, adiposity and aging.
Metabolism
39:
584-587,
1990[ISI][Medline].
9.
Corpas, E,
Harman SM,
and
Blackman MR.
Human growth hormone and human aging.
Endocr Rev
14:
20-39,
1993[Abstract].
10.
Cuneo, RC,
and
Wallace JD.
Growth hormone, insulin-like growth factors and sport.
Endocrinol and Metab
1:
3-13,
1994.
11.
Davidson, MB.
The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly.
Metabolism
28:
687-705,
1979.
12.
DeFronzo, RA.
Glucose intolerance in aging. Evidence for tissue insensitivity to insulin.
Diabetes
28:
1095-1101,
1979[ISI][Medline].
13.
Deuschle, M,
Blum WF,
Frystyk J,
Orskov H,
Schweiger U,
Weber B,
Korner A,
Gotthardt U,
Schmider J,
Standhardt H,
and
Heuser I.
Endurance training and its effect upon the activity of GH-IGFs system in elderly.
Int J Sports Med
19:
250-254,
1998[ISI][Medline].
14.
Eliakim, A,
Brasel JA,
Mohan S,
Barstow T,
Berman N,
and
Cooper DM.
Physical fitness, endurance training and the growth hormone-insulin-like growth factor I system in adolescent females.
J Clin Endocrinol Metab
81:
3986-3992,
1996[Abstract].
15.
Eliakim, A,
Brasel JA,
Mohan S,
Wong WLT,
and
Cooper DM.
Increased physical activity and the growth hormone-IGF-I axis in adolescent males.
Am J Physiol Regul Integr Comp Physiol
275:
R308-R314,
1998
16.
Finkelstein, J,
Roffwarg H,
Boyar P,
Kream J,
and
Hellman L.
Age-related changes in the twenty-four hour spontaneous secretion of growth hormone in normal individuals.
J Clin Endocrinol Metab
35:
665-670,
1972[ISI][Medline].
17.
Houmard, JA,
Egan PC,
Neufer PD,
Friedman JE,
Wheeler WS,
Israel RG,
and
Dohm GL.
Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men.
Am J Physiol Endocrinol Metab
261:
E437-E443,
1991
18.
Hellenius, ML,
Brisman KE,
Berglund BH,
and
De Faire HH.
Effects on glucose tolerance, insulin secretion, insulin-like growth factor I and its binding protein, IGFBP-1, in a randomized controlled diet and exercise study in healthy, middle-aged men.
J Intern Med
238:
121-130,
1995[ISI][Medline].
19.
Hopkins, NJ,
Jakeman JM,
Hughes SC,
and
Holly JMP
Changes in circulating insulin-like growth factor-binding protein-1 (IGFBP-1) during prolonged exercise: effect of carbohydrate feeding.
J Clin Endocrinol Metab
79:
1887-1890,
1994[Abstract].
20.
Jahreis, PJ,
Kauf E,
Fröhner G,
and
Schimdt HE.
Influence of intensive exercise on insulin-like growth factor 1, thyroid and steriod hormones in females gymnasts.
Growth Regul
1:
95-99,
1991[ISI][Medline].
21.
Koziris, LP,
Hickson RC,
Chatterton RT,
Groseth RT,
Christie JM,
Goldflies DG,
and
Unterman TG.
Serum levels of total and free IGF-I and IGFBP-3 are increased and maintained in long-term training.
J Appl Physiol
86:
1436-1442,
1999
22.
Kelly, PJ,
Eisman JA,
Stuart MC,
Pocock NA,
Sambrook PN,
and
Gwinn TH.
Somatomedin-C, physical fitness, and bone density.
J Clin Endocrinol Metab
70:
718-723,
1990[Abstract].
23.
Lewitt, MS,
Denyer GS,
Cooney GJ,
and
Baxter RC.
Insulin-like growth factor-binding protein-1 modulates blood glucose levels.
Endocrinology
129:
2254-2256,
1991[Abstract].
24.
Luger, A,
Watschinger B,
Deuster P,
Svoboda T,
Clodi M,
and
Chrousos GP.
Plasma growth hormone and prolactin responses to graded levels of acute exercise and to a lactate infusion.
Neuroendocrinology
56:
112-117,
1992[ISI][Medline].
25.
Lukaski, HC,
Johnson PE,
Bolonchuch WW,
and
Lykken V.
Assessment of fat-free mass using bioelectrical impedance measurements of the human body.
Am J Clin Nutr
41:
810-817,
1985[Abstract].
26.
Manetta, J,
Brun JF,
Callis A,
Mercier J,
and
Préfaut C.
Non-insulin-dependent glucose disposal in middle-aged and young athletes versus sedentary men.
Metabolism
50:
349-354,
2001[ISI][Medline].
27.
Manetta, J,
Brun JF,
Mercier J,
and
Préfaut C.
The effects of exercise training intensification on glucose disposal in elite cyclists.
Int J Sports Med
21:
338-343,
2000[ISI][Medline].
28.
Marcus, R,
Butterfield G,
Holloway L,
Gilliland L,
Baylink DJ,
Hintz RL,
and
Sherman BM.
Effects of short term administration of recombinant human growth hormone to elderly people.
J Clin Endocrinol Metab
70:
519-526,
1990[Abstract].
29.
Näveri, H.
Blood hormone and metabolite levels during graded ergometer exercise.
Scand J Clin Lab Invest
45:
599-603,
1985[ISI][Medline].
30.
Nguyen, UN,
Mougin F,
Simon-Rigaud ML,
Rouillon JD,
Marguet P,
and
Regnard J.
Influence of exercise duration on insulin-like growth factor and its binding proteins in athletes.
Eur J Appl Physiol
78:
533-537,
1998.
31.
Nyomba, BLG,
Berard L,
and
Murphy LJ.
Free insulin-like growth factor I (IGF-I) in healthy subjects: relationship with IGF-binding proteins and insulin sensitivity.
J Clin Endocrinol Metab
82:
2177-2181,
1997
32.
Pavlov, EP,
Harman SM,
Merriam GR,
Gelato MC,
and
Blackman MR.
Responses of growth hormone (GH) and somatomedin-C to GH-releasing hormone in healthy aging men.
J Clin Endocrinol Metab
62:
595-600,
1986[Abstract].
33.
Poehlman, ET,
and
Copeland KC.
Influence of physical activity on insulin-like growth factor-1 in healthy younger and older men.
J Clin Endocrinol Metab
71:
1468-1473,
1990[Abstract].
34.
Poehlman, ET,
Rosen CJ,
and
Copeland KC.
Influence of endurance training on insulin-like growth factor-I in older individuals.
Metabolism
43:
1401-1405,
1994[ISI][Medline].
35.
Rajkumar, K,
Dheen ST,
and
Murphy LJ.
Hyperglycemia and impaired glucose tolerance in IGF binding protein-1 transgenic mice.
Am J Physiol Endocrinol Metab
270:
E565-E571,
1996
36.
Rutamen, EM,
Pekonen F,
and
Mäkinen T.
Soluble 34K binding protein inhibits the binding of insulin-like growth factor I to its cell receptors in human secretory phase endometrium: evidence for autocrine/paracrine regulation of growth factor action.
J Clin Endocrinol Metab
66:
266-272,
1998[Abstract].
37.
Suikkari, AM,
Sane T,
Seppälä M,
and
Yki-Järvinen H.
Prolonged exercise increases serum insulin-like growth factor-binding protein concentration.
J Clin Endocrinol Metab
68:
141-144,
1989[Abstract].
38.
Tuomilehto, J,
Lindström J,
Eriksson JG,
Valle TT,
Hämäläinen H,
Ilanne-Parikka P,
Keinänen-Kiukaanniemi S,
Laakso M,
Louheranta A,
Rastas M,
Salminen V,
and
Uusitupa M, for the Finnish Diabetes Prevention Study Group
Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.
N Engl J Med
344:
1343-1350,
2001
39.
Zadik, Z,
Chalew SA,
McCarter RJ,
Meistas MM,
and
Kowarski AA.
The influence of age on the 24-hour integrated concentration of growth hormone in normal individuals.
J Clin Endocrinol Metab
60:
513-516,
1985[Abstract].