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Department of Physiology, University of Cape Town Medical School, Observatory 7925, South Africa
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ABSTRACT |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Trained cyclists with low muscle glycogen (LGH; n = 8) or normal glycogen (NGH; n = 5) exercised for 145 min at 70% of maximal oxygen uptake during a hyperglycemic clamp. Respiratory exchange ratio was higher in NGH than LGH, and free fatty acid concentrations were lower in NGH than LGH. Areas under the curve for insulin and lactate were lower in LGH than NGH. Total glucose infusion and total glucose oxidation were not different between NGH and LGH, and total glucose oxidation amounted to 65 and 66% of total glucose infusion in NGH and LGH, respectively. Rates of glucose oxidation rose during exercise, reaching peaks of 9.2 ± 1.7 and 8.3 ± 1.1 mmol/min in NGH and LGH, respectively. Muscle glycogen disappearance was greater in NGH than LGH. Thus 1) low muscle glycogen content does not cause increased glucose oxidation, even during hyperglycemia; instead there is an increase in fat oxidation, 2) there is an upper limit to the rate of glucose oxidation during exercise with hyperglycemia irrespective of muscle glycogen status, and 3) net muscle glycogen utilization is determined by muscle glycogen content at the start of exercise, even during hyperglycemia.
glycogenolysis; glucose oxidation
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INTRODUCTION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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COMPARED WITH MAINTENANCE of euglycemia, maintenance of hyperglycemia by glucose infusion results in an increase in glucose oxidation during exercise in subjects with normal glycogen content (5). However, the rate of glucose infusion exceeds the rate of glucose oxidation (5). In the companion study in this laboratory with subjects with low muscle glycogen content at the start of exercise (13), a similar discrepancy was noted during exercise with hyperglycemia. In accordance with the higher rate of oxidation in the hyperglycemic subjects, respiratory exchange ratio (RER) in the hyperglycemic subjects with low muscle glycogen content was higher than that in euglycemic subjects with low muscle glycogen content. However, RER of the hyperglycemic subjects was not different from that of subjects with normal glycogen content in whom euglycemia was maintained during the same exercise protocol. However, despite a significantly lower RER in low-glycogen euglycemic subjects than in subjects with normal muscle glycogen content, the rate of glucose oxidation did not differ and matched the rate of infusion.
Thus the effects of glucose concentration on RER and glucose oxidation rate are known for both normal and low-glycogen states, as is the effect of glycogen status during euglycemic conditions. However, the effect of glycogen content on RER and glucose oxidation rate in hyperglycemia is not known. Thus the aim of the current study was to investigate whether RER in subjects with normal muscle glycogen content would be the same as or higher than and whether glucose oxidation would be similar to or lower in subjects with low glycogen content if hyperglycemia were maintained in both groups during exercise. To answer this question, an almost identical protocol was followed as described in our companion study in hyperglycemic subjects with low muscle glycogen content (13), except that subjects in this study had normal muscle glycogen content and were compared with data of the hyperglycemic, low glycogen subjects in the companion study (13).
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METHODS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Five endurance-trained male cyclists participated in the study. The
protocol followed was identical to that followed in the companion study
(13) in that subjects performed an incremental exercise test to
exhaustion to determine maximal oxygen uptake (
O2 max) of each
subject, rested for 20 min, and then rode for a further 90 min at 70%
O2 max with 5-min
intervals at 90%
O2 max every 20 min
to deplete muscle glycogen. After this procedure, subjects followed
their normal diet and were instructed to do only light training on the
second day (~1 h of low-intensity cycling) to allow repletion of
muscle glycogen content to normal (NGH).
The experimental protocol on the third day was identical to that
followed with the hyperglycemic, low-glycogen content subjects in the
companion study (13). In both groups, plasma glucose concentration was
maintained at ~9 mmol/l during 145 min of exercise on a cycle
ergometer at 70% of
O2 max by
infusing a 25% mass/vol glucose solution using the
hyperglycemic glucose clamp technique described in detail previously
(13).
Measurements were taken, and laboratory analyses were identical to the procedures described in our companion study (13).
Statistical treatment. For the sake of clarity, results are presented along with those of the group with low muscle glycogen content in whom hyperglycemia was maintained (LGH) from the companion study (13). All results are presented as means ± SE. Statistical significance (P < 0.05) of between-group differences was assessed by a two-way analysis of variance (ANOVA) with repeated measures over time, followed by a Tukey's honest significant difference test for unequal n. An unpaired t-test was used for single data. For some measurements in which convergence of data in the second half of the trial resulted in masking of significant differences on the ANOVA, an unpaired t-test was used to compare area under the curve (AUC) measurements.
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RESULTS |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Subject characteristics are given in Table 1. There were no significant differences between groups in any of these parameters.
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Values for the rate of oxygen consumption
(O2) and rates (g/min) of fat
and carbohydrate oxidation during exercise are given in Table
2, and total (g) fat oxidation and total
carbohydrate oxidation for 145 min of exercise are given in Table
3.
O2 did not differ
significantly between groups and did not change significantly over the
duration of the trial, as the workload was maintained at 70% of
O2 max.
RER (Fig. 1) and total carbohydrate oxidation (Table 3) were significantly lower and total fat oxidation (Table 3) was significantly higher in LGH than in NGH
(P < 0.05). The rate of fat
oxidation (Table 2) was significantly higher, and the rate of
carbohydrate oxidation (Table 2) was lower in LGH than in NGH until 85 and 125 min, respectively (P < 0.05), but the change in RER, rate of carbohydrate oxidation, and rate of fat oxidation over the duration of the trial in NGH was not statistically significant. Free fatty acid concentrations (Fig. 2A) were
significantly higher in LGH than in NGH
(P < 0.05) throughout exercise.
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Mean plasma glucose concentrations (Fig.
3A)
after 5 min of exercise were 9.0 ± 0.1 and 9.5 ± 0.1 mmol/l for
LGH and NGH, respectively, with a coefficient of variation within
groups of 3 and 4%, respectively. Plasma insulin concentrations did
not change significantly over the duration of exercise in either group, but the AUC for insulin (Fig. 2B)
was significantly (P < 0.05) less in
LGH than in NGH. There were no significant differ ences between groups
in concentrations of plasma glucagon (Fig.
3B), norepinephrine (Fig.
2C), or growth hormone. The latter
showed great variability between subjects, especially in NGH (AUC 1,507 ± 342 vs. 4,930 ± 2,419 mU · l
1 · min1
for LGH vs. NGH, respectively).
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The rate of glucose infusion required to maintain blood glucose concentrations at ~9 mmol/l is shown in Fig. 4A and increased significantly throughout the trial in both groups (P < 0.05). The total amount of glucose infused during the 145 min of exercise (Fig. 5) was 1,484 ± 125 and 1,529 ± 86 mmol in LGH and NGH, respectively. This was not significantly different.
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Rates of glucose oxidation (Fig. 4B) increased progressively (P < 0.05) in both groups until 85 min, when a plateau was reached in NGH. In LGH, a plateau was also reached 20 min later. Peak rates of glucose oxidation were 8.3 ± 1.1 and 9.2 ± 1.7 mmol/min (1.51 ± 0.19 and 1.66 ± 0.31 g/min) in LGH and NGH, respectively. Total glucose oxidation (Fig. 5) did not differ significantly between LGH and NGH (840 ± 74 vs. 987 ± 111 mmol; 151 ± 13 vs. 177 ± 20 g). In both groups, the total amount of glucose oxidized was significantly lower than the total amount of glucose infused (66 vs. 65% in LGH and NGH, respectively; Fig. 5).
The contribution of glucose to total carbohydrate oxidation did not differ between groups and increased significantly (P < 0.05) until 125 min to 53 ± 5% in NGH and until 105 min to 58 ± 5% in LGH, whereafter it remained relatively constant. There was also no significant difference between groups in the contribution of glucose oxidation to total energy, which reached peaks of 41 ± 4 and 44 ± 5% in LGH and NGH, respectively, after 105 min.
Muscle glycogen concentrations (Table 3) were significantly higher at the start of exercise in NGH than LGH. Muscle glycogen disappearance (Fig. 6) was greater (P < 0.05) in NGH than LGH (78 ± 22 and 41 ± 4 mmol/kg wet wt, respectively). There were no significant differences in muscle glycogen concentrations between groups at the end of exercise (Table 3). Plasma lactate concentrations (Fig. 7) were significantly (P < 0.05) lower throughout exercise in LGH than in NGH.
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DISCUSSION |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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The most significant findings in this study are that, despite differences in muscle glycogen content, glucose oxidation was not different between NGH and LGH (Figs. 4 and 8) and that low muscle glycogen content resulted in a shift toward lipid oxidation (Figs. 1 and 8), even under conditions of hyperglycemia (Fig. 5).
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RER was lower during exercise in LGH subjects than in NGH (Fig. 1). Because glucose oxidation did not differ between groups during exercise (Fig. 3A), it is apparent that the lower RER in LGH must have been as a result of low muscle glycogen content. In addition, the shift toward lipid oxidation with low muscle glycogen content cannot be fully overcome by glucose infusion, even when the rate of infusion exceeds the rate of oxidation (Figs. 5 and 6) and blood glucose concentration is two times normal. The slight, although not significant, decrease in RER in NGH during exercise can be attributed to the decline in muscle glycogen content in that group during exercise.
As found in our companion study in this laboratory in euglycemic subjects (13), there was no difference in rates of glucose oxidation between these hyperglycemic subjects with either low (LGH) or normal (NGH) muscle glycogen content. Similar to the findings of Hawley et al. (5) in subjects with normal muscle glycogen content, total glucose oxidation was significantly lower than the total amount of glucose infused (Fig. 5) in both NGH and LGH. The reason for this apparent upper limit in glucose oxidation is probably that the exercise intensity was simply not high enough to elicit a greater increase in the rate of carbohydrate oxidation (10). Thus glucose oxidation is not increased by reduced muscle glycogen content in subjects with similar blood glucose concentrations; instead, a switch takes place toward lipid oxidation even when plasma glucose concentrations are hyperglycemic. This strengthens the argument in our previous study (13) that this may be a teleological mechanism to compensate for a reduced availability of intramuscular carbohydrate availability without predisposing to hypoglycemia.
The significant difference between LGH and NGH during exercise in the AUC for insulin (Fig. 2B) suggests that, even during hyperglycemia, plasma insulin concentrations are influenced by muscle glycogen content. In the current study, glucose uptake by the muscle in LGH was possibly limited by the lower insulin (6, 14) and higher free fatty acid (1) concentrations (Fig. 2, A and B) in these subjects compared with NGH. Hyperinsulinemia increases glucose uptake during hyperglycemia at rest (2, 11); thus, even though both groups were hyperglycemic, the lower plasma insulin concentrations in LGH may explain why total glucose oxidation was not increased in LGH relative to NGH to compensate for the reduced availability of muscle glycogen. In contrast to the companion study in euglycemic subjects with either normal or low muscle glycogen content (13), norepinephrine concentrations were not significantly different between groups in the current study (Fig. 2C).
As discussed in our previous study (13), the lower RER and higher free fatty acid concentration in the current study (Figs. 1 and 2C) during exercise in subjects with low muscle glycogen content (LGH) are similar to those found in patients with muscle phosphorylase deficiency (McArdle's disease; see Refs. 7, 12). Because studies of McArdle's disease link the metabolic and cardiovascular defects of this disease with neural feedback from chemoreceptors in contracting muscle (7, 8, 12), the failure to restore RER in subjects with low muscle glycogen content with a glucose infusion to that found in similarly hyperglycemic subjects with normal muscle glycogen content suggests that there may be similar metabolic signaling from the muscle.
The greater muscle glycogen disappearance in subjects with a higher muscle glycogen content at the start of exercise (Fig. 6) was reflected in higher plasma lactate concentrations in NGH than in LGH (Fig. 7). This is similar to a number of studies that have found that higher muscle glycogen content at the start of exercise results in a greater rate of muscle glycogen utilization during exercise (3, 4, 9), which does not appear to be influenced by the availability of plasma glucose.
In conclusion, this study showed that
1) when exercise is started with low
muscle glycogen content but without concomitant fatigue, exogenous
glucose provided to maintain hyperglycemia is not used to any greater
extent than when muscle glycogen content is normal, but instead the
energy deficit is made up by an increase in fat oxidation;
2) there is an upper limit to the
rate of glucose oxidation during exercise at 70% of
O2 max with
hyperglycemia irrespective of muscle glycogen status; and
3) net muscle glycogen utilization
is determined by the muscle glycogen content at the start of exercise
even when hyperglycemia is maintained during exercise.
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ACKNOWLEDGEMENTS |
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We thank Gary Wilson and Judy Belonje for technical assistance and Drs. Wayne Derman and Martin Schwellnus for performing the muscle biopsies.
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FOOTNOTES |
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This study was supported by grants from the South African Sugar Association, the South African Medical Research Council, and the Nellie Atkinson and Harry Crossley Research Funds of the University of Cape Town.
Address for reprint requests: A. N. Bosch, Bioenergetics of Exercise Research Unit, Sports Science Institute of South Africa, Newlands 7700, South Africa.
Received 11 November 1996; accepted in final form 22 September 1997.
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REFERENCES |
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Top
Abstract
Introduction
Methods
Results
Discussion
References
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Rate of
glucose infusion significantly higher than rate of glucose oxidation
(P < 0.05).
