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Vol. 84, Issue 4, 1480-1482, April 1998
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ABSTRACT |
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Top
Abstract
Letter
References
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The following is the abstract of the article discussed in the subsequent letter:
Friedlander, Anne L., Gretchen A. Casazza, Michael
A. Horning, Melvin J. Huie, and George A. Brooks. Training-induced alterations of glucose flux in men. J. Appl. Physiol. 82(4):
1360-1369, 1997.
We examined the hypothesis that glucose flux was
directly related to relative exercise intensity both before and after a 10-wk cycle ergometer training program in 19 healthy male subjects. Two
pretraining trials [45 and 65% of peak O2 consumption
(
O2 peak)] and two post-
training trials (same absolute and relative intensities as 65%
pretraining) were performed for 90 min of rest and 1 h of cycling
exercise. After training, subjects increased
O2 peak by 9.4 ± 1.4%. Pretraining, the intensity effect on glucose kinetics was
evident with rates of appearance (Ra; 5.84 ± 0.23 vs.
4.73 ± 0.19 mg · kg
1 · min1),
disappearance (Rd; 5.78 ± 0.19 vs. 4.73 ± 0.19
mg · kg1 · min1),
oxidation (Rox; 5.36 ± 0.15 vs. 3.41 ± 0.23
mg · kg1 · min1),
and metabolic clearance (7.03 ± 0.56 vs. 5.20 ± 0.28
ml · kg1 · min1)
of glucose being significantly greater (P 
0.05) in the
65% than the 45%
O2 peak trial. When
Rd was expressed as a percentage of total energy expended
per minute (Rd E), there was no difference between the
45 and 65% intensities. Training did reduce
Ra(4.63 ± 0.25), Rd(4.65 ± 0.24),
Rox(3.77 ± 0.43), and Rd E
(15.30 ± 0.40 to 12.85 ± 0.81) when subjects were tested at the
same absolute workload (P 0.05). However, when they were
tested at the same relative workload, Ra, Rd,
and Rd E were not different, although Rox
was lower posttraining (5.36 ± 0.15 vs. 4.41 ± 0.42,
P 0.05). These results show 1) glucose use is
directly related to exercise intensity; 2) training decreases
glucose flux for a given power output; 3) when expressed as
relative exercise intensity, training does not affect the magnitude of
blood glucose use during exercise; 4) training alters the
pathways of glucose disposal.
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LETTER |
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Abstract
Letter
References
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Training-Induced Alterations in Glucose Metabolism During Exercise
To the Editor: Friedlander et al. (8) have confirmed our findings that endurance training reduces glucose appearance, disappearance, and oxidation rates (Ra, Rd, and Rox, respectively) during moderate exercise performed at the same absolute power output before and after training (4). Their data also corroborate our report that the training-induced decrease in Ra is due, in part, to a decrease in the rate of gluconeogenesis (6). Finally, their Rox data agree with our conclusion, based on cross-sectional observations, that training reduces glucose utilization even when the exercise is performed at the same relative intensity [i.e., at the same percentage of peak O2 uptake (O2 peak)], as in the
untrained state (5). Paradoxically, however, Friedlander et al. (8) did
not find any training-induced changes in Ra/Rd
under the latter conditions, leading them to conclude that "...
when expressed as relative exercise intensity, training does not affect
blood glucose flux... ." Instead, they argue that training
affects the pathways of glucose disposal, possibly by enhancing muscle
glycogen synthesis during exercise.
I believe that there is a simpler explanation for their findings. As we
(5, 6) and others have done, Friedlander et al. (8) increased the rate
of tracer infusion (F) at the onset of exercise to minimize
changes in glucose enrichment. In contrast to previous studies,
however, they did not use the same F under all conditions.
Instead, they increased F fourfold during exercise at 65% of
O2 peak after training,
compared with only threefold in the other three trials. As shown
previously (2, 7), the magnitude of the step increase in F has
a direct impact on the calculated Ra during exercise.
Importantly, this is true, even though an apparent plateau in plasma
enrichment may be obtained (2). The reason for this is that, even
though exercise increases the rate of glucose exchange between various
pools in the body (3), considerable time is still required before
complete reequilibration of the tracer is achieved. For example, a
computer simulation (MLAB, Civilized Software, Bethesda, MD) using the
latter compartmental modeling data indicates that ~90 min would be
required to reach a new steady state in plasma enrichment at 65% of
O2 peak [i.e., the
intensity used by Friedlander et al. (8)]. Because the increase in
F and its ultimate effect on plasma enrichment are dissociated
with respect to time, yet the increase in F enters immediately
into the calculations, a larger step increase in F results in a
higher estimated Ra, even when it is calculated by using
the non-steady-state Steele equation. Because Friedlander et al.
increased F fourfold after training vs. only threefold before
training, it is likely that they overestimated Ra after training compared with before training and, consequently,
underestimated the change due to training. Indeed, both the computer
simulation and my unpublished observations suggest that, because of the
difference in tracer-infusion protocols, Ra was biased
upward by ~15% after training compared with before training, such
that Friedlander et al. missed a similar percent decrease in
Ra (and thus Rd) due to training. An ~15%
lower Ra and Rd during exercise at 65% of O2 peak after training
would agree quite nicely with their finding that training reduced
Rox by ~18% under these conditions (the calculated
Rox would be much less affected by the difference in F, because of the intervening effect of the multiple-pool
bicarbonate system). This interpretation also agrees with the fact that
when the subjects exercised at the same absolute intensity as before training (i.e., at 58% of their new, higher
O2 peak), their Ra and Rd were the same as when they had
exercised at 45% of
O2 peak before training.
In other words, Friedlander et al.'s (8) own data show that, when
F is the same, a higher relative exercise intensity is required
after training to elicit the same response in Ra and
Rd.
Despite this limitation in experimental design, the study of Friedlander et al. (8) seemingly refutes the most important new tenet of Brooks' and Mercier's "crossover" concept, which is the prediction that "... after endurance training blood glucose appearance rate and the rate of hepatic gluconeogenesis are increased... ." during intense exercise at the same relative intensity (1). Perhaps the authors would like to comment on this issue.
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REFERENCES |
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Top
Abstract
Letter
References
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1.
Brooks, G. A.,
and
J. Mercier.
Balance of carbohydrate and lipid utilization during exercise: the "crossover" concept.
J. Appl. Physiol.
76:
2253-2261,
1994
2.
Coggan, A. R.
Plasma glucose metabolism during exercise in humans.
Sports Med.
11:
102-124,
1991[Medline].
3.
Coggan, A. R.,
D. L. Chinkes,
A. Gastaldelli,
and
K. D. Tipton.
Exercise increases the rate of glucose exchange between plasma and interstitial fluid (Abstract).
FASEB J.
10:
A1652,
1996.
4.
Coggan, A. R.,
W. M. Kohrt,
R. J. Spina,
D. M. Bier,
and
J. O. Holloszy.
Endurance training decreases plasma glucose turnover and oxidation during moderate-intensity exercise in men.
J. Appl. Physiol.
68:
990-996,
1990
5.
Coggan, A. R.,
C. A. Raguso,
B. D. Williams,
L. S. Sidossis,
and
A. Gastaldelli.
Glucose kinetics during high-intensity exercise in endurance-trained and untrained humans.
J. Appl. Physiol.
78:
1203-1207,
1995
6.
Coggan, A. R.,
S. C. Swanson,
L. A. Mendenhall,
D. L. Habash,
and
C. L. Kien.
Effect of endurance training on hepatic glycogenolysis and gluconeogenesis during prolonged exercise in men.
Am. J. Physiol.
268 (Endocrinol. Metab. 31):
E375-E383,
1995
7.
Finegood, D. T.,
P. D. G. Miles,
H. L. A. Lickley,
and
M. Vranic.
Estimation of glucose production during exercise with a one-compartment variable-volume model.
J. Appl. Physiol.
72:
2501-2509,
1992
8.
Friedlander, A. L.,
G. A. Casazza,
M. A. Horning,
M. J. Huie,
and
G. A. Brooks.
Training-induced alterations in glucose flux in men.
J. Appl. Physiol.
82:
1360-1369,
1997
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Andrew Coggan Shriners Hospital for Children Burns Institute Galveston, Texas 77550-2725 |
To the Editor: We appreciate the opportunity to respond to
Coggan's letter, but we are confused by several aspects of it. At the
outset of his letter, Coggan claims that our results (6) are like his
(4), but then he goes on to criticize our methodology with reference to
his own work. An inspection of both Coggan's letter and paper (4)
reveals flaws in both.
Coggan criticizes our work by asserting that the magnitude of the step
increase in tracer infusion rate at the onset of exercise affects the
computed Ra during exercise, even after an "apparent plateau" in plasma isotopic enrichment (IE). He hypothesizes a slow
equilibration of tracer distribution after the onset of exercise and
predicts that a steady state in plasma enrichment in our experiment would require ~90 min, based on a computer simulation with
unspecified structure or parameters.
In assessing Coggan's assertion, it is important to consider our
design and examine the data. We used a steady-state design so that we
could calculate and report glucose flux rates after 30 min of exercise
when blood IE values were constant, or nearly so. Our Fig. 1 shows IE
as a function of time. In none of the records does IE continue to
increase after 30 min of exercise, as Coggan predicts. In three of four
experimental conditions, IE is constant during the last 30 min of
exercise, the period during which we computed Ra.
Examination of the data shows that this is a statistical fact, not just
an "apparent plateau." In steady state, the magnitude of the
infusion rate F does not affect the computed Ra: a
larger F causes a proportionally larger enrichment. In the
fourth experimental condition [65% of
Without an adequate description of the computer simulation mentioned by
Coggan in his letter, it is difficult to comment on any errors he might
have made. That mistakes were made is clear when the data (Fig. 1, showing IE stabilized in 30 min) are compared with the model prediction
(90 min). Furthermore, a direct experimental test also denies Coggan's
hypothesis: in a parallel experiment, performed on nine different
subjects, but with a step to four times the resting F during
exercise trials eliciting 65% of
In contrast to our results (6), in which F was held constant in
subjects during steady-rate exercise, are those of Coggan et al. (4).
By varying the isotope infusion rate continuously during their
experiments, Coggan and associates created the worst possible scenario.
Exercise power output and metabolic rate
( In our study, tracer-measured blood glucose Ra rose rapidly
at the start of exercise and then plateaued, perhaps rising slowly over
time. Splanchnic (hepatic) glucose release is, unfortunately, infrequently measured, but the data available on humans (11) and dogs
(12) show the same pattern as we observed. Moreover, reports on human
limb glucose net uptake during exercise (7-9) show a similar
pattern of rapid adjustment at the outset of contractions, followed by
slow adjustment over time. In contrast, the experimental paradigm
employed by Coggan et al. (4) of ramping the F continuously produced the result of glucose Ra and Rd rising
linearly over time. In our view, this result was unphysiological and an
artifact of the methodology employed. Thus the relatively small
differences between athletes and nonathletes observed by Coggan et al.
need to be viewed with a degree of uncertainty.
Irrespective of methodological differences, from the physiological
standpoint, an important point addressed by Coggan et al. (4) and us
(6) is that of the effect of chronic physical activity on glucose
kinetics. We utilized a longitudinal design and studied healthy young
men before and after training; in contrast, Coggan et al. (4) compared
responses in athletes and nonathletes. We note that it is generally
recognized that physiological and metabolic responses in athletes are
distinct from those of nonathletes (1). Consequently, it is seldom
asserted that responses of athletes to any condition uniquely
demonstrate the effects of environment (i.e., training), as opposed to
the interactive effects of environment and genetics.
From the scientific standpoint, we would like to be able to state that
the effects of training on glucose flux are sufficiently robust that
they are demonstrable when a variety of designs and experimental
approaches is used. It is our position that the more recent data
obtained on humans by using stable-isotope tracers are similar to those
obtained previously by us on laboratory animals (2). Thus we are
confident about the generality of the findings. We do acknowledge that
it is Coggan's right to object to our position and we view his
objections as useful, since they focus debate on key issues, even if we
find his objections groundless.
Finally, with regard to Coggan's objections to the "crossover"
concept (3), we remain confident that data obtained from measurements
of respiratory gas exchange, isotopic tracers, muscle biopsies, and
arteriovenous concentration differences in humans and other mammals (2,
4, 6-9) show crossover to carbohydrate dependency during exercises
eliciting 50% maximal
REPLY
Top
Abstract
Letter
References
O2 peak
pretraining], the IE was not constant but fell in the
last 30 min of exercise. We used the Steele equation (10) to compute
the non-steady-state Ra in this case. It is important to
recognize that the variable-volume model cited in Coggan's letter (5)
accounts for the effect of the declining Ra in exactly the
same way: the declining IE leads to a larger estimate of
Ra. It should be noted that in this experimental condition
the step in F was insufficient to maintain a constant IE. This
decline in IE after a peak, and a corresponding increase in the
estimate of Ra, are just the opposite of the effect hypothesized by Coggan.
O2 peak, pre- and
posttraining, we (B. C. Bergman, G. E. Butterfield, G. A. Casazza, M. A. Horning, E. E. Wolfel, and G. A. Brooks, unpublished observations)
reproduced our previously published glucose flux rates
(6).
O2) were constant as was
blood glucose concentration. However, by grading the isotope infusion
rate over time, Coggan et al. ensured a changing blood IE, slow and
continuously changing tracer mixing in various compartments, and
constantly changing (calculated) glucose Ra and
Rd. In other words, Coggan et al. turned a steady-state metabolic condition into a nonsteady isotope tracer condition, an
unfortunate situation, which complicated and compromised calculation of
glucose fluxes.
O2, regardless of
training status.
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REFERENCES |
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Top
Abstract
Letter
References
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1.
Bouchard, C.,
and
L. Perusse.
Heredity, activity level, fitness, and health.
In: Physical Activity, Fitness, and Health, edited by C. Bouchard,
R. J. Shepard,
and T. Stevens. Champaign, IL: Human Kinetics, 1994, p. 106-118.
2.
Brooks, G. A.,
and
C. M. Donovan.
Effect of training on glucose kinetics during exercise.
Am. J. Physiol.
244 (Endocrinol. Metab. 7):
E505-E512,
1983
3.
Brooks, G. A.,
and
J. Mercier.
The balance of carbohydrate and lipid utilization during exercise: the "crossover" concept.
J. Appl. Physiol.
76:
2253-2261,
1994.
4.
Coggan, A. R.,
C. A. Raguso,
B. D. Williams,
L. S. Sidossis,
and
A. Gastaldelli.
Glucose kinetics during high-intensity exercise in endurance-trained and untrained humans.
J. Appl. Physiol.
78:
1203-1207,
1995.
5.
Finegood, D. T.,
P. D. G. Miles,
H. L. A. Lickley,
and
M. Vranic.
Estimation of glucose production during exercise with a one-compartment variable-volume model.
J. Appl. Physiol.
72:
2501-2509,
1992.
6.
Friedlander, A. L.,
G. A. Casazza,
M. A. Horning,
M. J. Huie,
and
G. A. Brooks.
Training-induced alterations of glucose flux in men.
J. Appl. Physiol.
82:
1360-1369,
1997.
7.
Kiens, B.,
B. Essen-Gustavson,
N. J. Christensen,
and
B. Saltin.
Skeletal muscle substrate utilization during submaximal exercise in man: effects of endurance training.
J. Physiol. (Lond.)
469:
459-478,
1993
8.
Kjaer, M.,
B. Kiens,
M. Hargreaves,
and
E. A. Richter.
Influence of active muscle mass on glucose homeostasis during exercise.
J. Appl. Physiol.
71:
552-557,
1991
9.
Roberts, A. C.,
J. T. Reeves,
G. E. Butterfield,
R. S. Mazzeo,
J. R. Sutton,
E. E. Wolfel,
and
G. A. Brooks.
Altitude and 
-blockade augment glucose utilization during exercise.
J. Appl. Physiol.
80:
605-615,
1996
10.
Steele, R.
Influence of glucose loading and injected insulin on hepatic glucose output.
Ann. NY Acad. Sci.
82:
420-430,
1959.
11.
Wahren, J.,
P. Felig,
G. Ahlborg,
and
L. Jorfeldt.
Glucose metabolism during leg exercise in man.
J. Clin Invest.
50:
2715-2725,
1971.
12.
Wasserman, D. H.,
D. B. Lacey,
D. R. Green,
P. E. Williams,
and
A. D. Cherrington.
Dynamics of hepatic lactate and glucose balances during prolonged exercise and recovery in the dog.
J. Appl. Physiol.
63:
2411-2417,
1987
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George A. Brooks Anne L. Friedlander Exercise Physiology Laboratory Department of Integrative Biology University of California, Berkeley Berkeley, California 94720-4480 |
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