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Journal of Physiology (2002), 542.2, pp. 403-412
© Copyright 2002 The Physiological Society
DOI: 10.1113/jphysiol.2002.018135

Myocardial and skeletal muscle glucose uptake during exercise in humans

Jukka Kemppainen *, Toshihiko Fujimoto*†, Kari K. Kalliokoski *, Tapio Viljanen*, Pirjo Nuutila*‡ and Juhani Knuuti *

	ABSTRACT

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The purpose of this study was to investigate the effects of exercise on myocardial glucose uptake and whether the pattern of glucose uptake is the same as in skeletal muscle. Glucose uptake was measured using positron emission tomography (PET) and 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG). Twelve healthy men were studied during rest, while 14 subjects were studied after 35 min of bicycle exercise corresponding to 30, 55 and 75 % of maximal oxygen consumption (_O2,max) on three separate days. [¹⁸F]FDG was injected 10 min after the start of exercise and exercise continued for a further 25 min. Myocardial and skeletal muscle PET scanning was commenced directly after the completion of the exercise bout. As compared to the resting state, exercise doubled myocardial glucose uptake at the 30 % (P = 0.056) and 55 % intensity levels (P < 0.05), while at the 75 % intensity level glucose uptake was reduced significantly compared to the lower exercise intensities. There was no significant difference between the highest intensity level and the resting state (P = 0.18). At rest and during low-intensity exercise, myocardial glucose uptake was inversely associated with circulating levels of free fatty acids. However, during higher exercise intensities when plasma lactate concentrations increased significantly, this association disappeared. In contrast to myocardial responses, skeletal muscle glucose uptake rose in parallel with exercise intensity from rest to 30 % and then 55 % _O2,max (P < 0.001) and tended to increase further at the intensity of 75 % _O2,max (P = 0.065). In conclusion, these results demonstrate that myocardial glucose uptake is increased during mild- and moderate-intensity exercise, but is decreased during high-intensity exercise. This finding suggests that the increased myocardial energy that is needed during high-intensity exercise is supplied by substrates other than glucose.

(Received 1 February 2002; accepted after revision 19 April 2002)
Corresponding author J. Knuuti: Turku PET Centre, PO Box 52, 20521 Turku, Finland. Email: juhani.knuuti{at}tyks.fi

	INTRODUCTION

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Limited data are available regarding the influence of different physiological exercise intensities on myocardial glucose uptake. It is not currently clear whether myocardial glucose uptake increases with increasing exercise intensity, as is seen in skeletal muscle (Kjaer et al. 1986). Gertz et al. (1988) reported that myocardial glucose uptake increased twofold during supine bicycle exercise performed at 40 % of maximal oxygen consumption (_O2,max), but they were unable to measure glucose uptake during high-intensity exercise due to methodological limitations. In the study of Camici et al. (1989), cardiac pacing increased myocardial glucose uptake in parallel with the increase in heart rate. However, cardiac pacing does not induce the same metabolic response that is obtained during physiological exercise.

The heart has a greater oxygen consumption both at rest and during exercise compared to skeletal muscle (Rowell, 1986). The greater demand for oxidative metabolism in the heart is compensated for by a greater mitochondrial volume and oxidative enzyme capacity, along with a greater activity of cardiac-type lactate dehydrogenase (Jansson & Sylven, 1986). Therefore, myocardial fuel preference during exercise may be different to that of skeletal muscle at different exercise intensities.

With regard to the difference in the oxidative capabilities of heart and skeletal muscle and lack of quantified myocardial glucose uptake data during aerobic and anaerobic exercise, it is physiologically relevant to study and compare myocardial and skeletal muscle glucose uptake during exercise of different intensities. The purpose of this study was to investigate the effect of exercise on myocardial glucose uptake and whether this glucose uptake pattern is similar in skeletal muscle. Therefore, myocardial and skeletal muscle glucose uptake was measured at rest and after low-, moderate- and high-intensity bicycle exercise using positron emission tomography (PET) and 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG). This approach allows a direct assessment of myocardial and skeletal muscle metabolism without interference from other tissues and without invasive cardiac catheterisation. Moreover, myocardial and skeletal muscle glucose uptake can be quantified within any given regions of interest (ROIs) in vivo.

	METHODS

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Subjects

Twenty-six well-conditioned, apparently healthy men participated in the study. The subject characteristics are presented in Table 1. The subjects were not taking any medications and were healthy as judged by their history, a physical examination and routine laboratory tests. The purpose and potential risks of this study were explained to the subjects and written informed consent to participate was obtained from them. The study was performed according to the Declaration of Helsinki and the joint Ethical Committee for the Turku University Central hospital and the University of Turku approved the study protocol.

Study design

The subjects were instructed to maintain a regular diet. They fasted for at least 12 h before the study and any kind of strenuous physical activity was prohibited for at least 1 day before the experiment. Subjects were divided into two groups, resting and exercising: 14 subjects participated in the exercise protocol and 12 subjects were studied only at rest. Each subject involved in the exercise protocol was studied on three separate days within 3 weeks with a minimum of 2 days separating each study day. The study design is illustrated in Fig. 1. Two catheters were inserted, one in an antecubital forearm vein for injection of [¹⁸F]FDG, and another in the opposite antecubital vein for sampling of arterialised venous blood. Plasma glucose samples were drawn at 0, 10, 20, 35, 50 and 60 min after the start of exercise. Serum insulin samples were drawn at 0, 35, 40, 50 and 60 min. The blood samples for cortisol, free fatty acids (FFAs) and lactate were drawn before and at the end of exercise, and after the heart PET scan. Arterialised venous blood samples for measurement of plasma radioactivity were obtained from the time of injection to the end of scan as follows: 10 samples within the first 3 min, thereafter samples at 4, 5, 7.5, 10, 20, 30, 40 and 50 min after the injection. At the beginning of the study, transmission scans of the femoral and thoracic regions were performed and the scanning areas were carefully marked on the skin. Subjects cycled (828E Monark, Sweden) on three separate days at workloads of 30, 55 or 75 % _O2,max at a pedal cadence of 60 r.p.m. After 10 min of exercise, [¹⁸F]FDG (156.2 ± 2.8 MBq) was injected, and the exercise continued thereafter for 25 min, giving a total exercise time of 35 min. PET imaging started immediately after the end of exercise. A 12 min static scan of the femoral region was performed, followed by a 12 min static scan of the thoracic region. In the group studied only at rest, skeletal muscle scans were performed on five subjects, while seven subjects completed the whole study protocol. PET scanning and blood sampling was carried out as in the exercise group.

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Figure 1. Study design The arrow indicates 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) injection 10 min after the beginning of exercise. Before and immediately after exercise, transmission and emission scans were obtained from the thoracic and femoral regions, respectively. Exercise duration was 35 min and the total study time was 120 min. PET, positron emission tomography; O2,max, maximal oxygen consumption.

PET tracer, image acquisition and processing

[¹⁸F]FDG was synthesised with an automatic apparatus by a modification of the method of Hamacher et al. (1986). The specific radioactivity at the end of the synthesis of [¹⁸F]FDG was ~74 GBq µmol^-1 and its radiochemical purity exceeded 98 %. An eight-ring ECAT 931/08-tomograph (Siemens/CTI, Knoxvill, TN, USA) with an axial resolution of 6.7 mm and an in-plane resolution of 6.5 mm was used. All data were corrected for deadtime, decay and measured photon attenuation. Static FDG scans were reconstructed into a 128 128 matrix using the median root prior (MRP) technique (Alenius & Ruotsalainen, 1997). The final in-plane resolution of the reconstructed images was 8 mm.

Regions of interest

For determination of myocardial glucose uptake, ROIs were drawn on four adjacent midventricular planes, with care taken to avoid the myocardial borders. ROIs within the quadriceps femoris (QF) were drawn on four adjacent planes in the middle of the QF between the patella and the spina iliaca anterior superior on both the left and right legs. The average value of these ROIs was used to calculate glucose uptake. Example ROIs are presented in Fig. 2.

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Figure 2. Myocardial and femoral PET images at rest, and during exercise at 30, 55 and 75 % O2,max The images are scaled to the fixed uptake level. Examples of regions of interest (ROIs) are presented on myocardium and skeletal muscle.

Calculation of regional glucose uptake

Quantification of glucose uptake was based on the method developed by Sokoloff et al. (1977). The rate of glucose uptake (rGU) is obtained by multiplying the fractional rate of tracer uptake (K_i) by the plasma glucose concentration ([Glc]_p) divided by a lumped constant term (LC): rGU = ([Glc]_p/LC) K_i. The LC accounts for differences in the transport and phosphorylation of [¹⁸F]FDG and glucose. An LC value of 1.2 was used for skeletal muscle (Kelley et al. 1999; Peltoniemi et al. 2000) and 1.0 was used for the myocardium (Ng et al. 1998). Since the PET scans were performed after exercise, we applied a simplified graphical analysis on the data. The K_i was calculated as C_m/C_p : (C_p)/C_p, where C_m is either myocardial or skeletal muscle radioactivity, C_p is plasma radioactivity concentration, and C_p is the integral of plasma radioactivity concentration from the time of injection to the end of the respective scan. Since the plasma radioactivity is very low 25 min after tracer injection and exercise, the period between the end of exercise and the start of the scan has a minor effect on myocardial and skeletal muscle tissue tracer counts. Thus, the measured K_i reflects the situation during exercise.

_O2,max measurement

_O2,max was determined for each subject using a continuous incremental cycle ergometer protocol and gas exchange analysis (Model 800S, Ergoline, Mijnhardt, The Netherlands). Individual aerobic and anaerobic thresholds were determined by lactate measurements during the test. Workloads for the PET studies were individually chosen to be 30, 55 and 75 % _O2,max.

Other measurements

Heart rate was monitored during the exercise using a heart rate monitor (Vantage XL, Polar Electro, Finland). Plasma glucose was determined by a glucose oxidase method (GM7 Analyser, Analox Instruments, Hammersmith, London, UK). Plasma lactate was determined by enzymatic analysis (Marbach & Weil, 1967). Serum free insulin concentrations were measured using a double-antibody radioimmunoassay (Pharmacia Insulin RIA kit, Pharmacia, Uppsala, Sweden) after precipitation with polyethylene glycol. Serum FFAs were determined with an enzymatic colorimetric method (Nefa C test, Wako Chemicals, Neuss, Germany), and serum cortisol concentrations by radioimmunoassay (Cortisol [¹²⁵I] Radioimmunoassay; Orion Diagnostica, Espoo, Finland).

Statistics

Statistical analysis was performed with the SAS statistical program package (SAS Institute, Cary, NC, USA ) and Microsoft Excel 97. A two-tailed Student's unpaired t test was used to determine whether there was a difference in myocardial or skeletal muscle glucose uptake between the group studied only at rest and the exercise group. An ANOVA followed by Tukey's Studentised range test was used to compare the effect of different exercise intensities. Non-linear regression analysis was used between myocardial glucose uptake and FFA levels because it described the relationship better, as documented previously (Nuutila et al. 1994). This analysis method was also used between myocardial glucose uptake and plasma lactate concentrations. Calculations of non-linear correlations were performed with Microsoft Excel 97. R² values were produced by exponential least-square fit. Critical r values for P < 0.05 were obtained from statistical tables. The results are expressed as means ± S.D.

	RESULTS

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Exercise parameters

The mean _O2,max in the exercise group was 49.6 ± 9.7 ml kg^-1 min^-1 and the maximal heart rate during the _O2,max test was 190 ± 9 beats min^-1. The average exercise intensities at 30, 55 and 75% _O2,max were 91 ± 24, 167 ± 38 and 226 ± 35 W, respectively. Heart rates at the end of exercise at these three intensities were 104 ± 8, 149 ± 16 and 177 ± 10 beats min^-1, respectively. There were significant differences in both the absolute values of exercise intensities and heart rates at each exercise intensity level (P < 0.001).

Metabolic parameters

The concentration of plasma glucose and serum insulin did not change during or after the exercise at 30 or 55 % _O2,max. Plasma glucose started to increase slightly towards the end of the 75 % _O2,max exercise period and was significantly higher at the end of the exercise, remaining slightly elevated for the subsequent 20 min (Fig. 3A). Concomitantly, serum insulin concentration doubled 5 min after the end of exercise at the highest exercise intensity as compared to pre-exercise values (Fig. 3B). Compared to basal values, plasma lactate concentrations did not increase significantly at the lowest exercise intensity, but increased by a factor of 3.6 and 9.4 at intensity levels of 55 and 75 % _O2,max, respectively (Fig. 3C). Changes in serum FFA concentrations were minor. Serum FFA concentrations increased significantly compared with baseline values at the end of the lowest-intensity exercise bout (Fig. 3D), while they remained unchanged at the other two exercise intensity levels. Serum cortisol remained unchanged during low-intensity exercise, but was significantly increased during the higher exercise intensities (Fig. 3E).

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Figure 3. Plasma glucose (A), serum insulin (B), plasma lactate (C ), serum free fatty acid (FFA; D), serum cortisol (E), and average plasma radioactivity concentrations (F ) from the start of the exercise period to the end of the PET scan during three different exercise intensities In A-F, data relating to the three exercise intensities imposed (30, 55 and 75 % O2,max) are indicated by , and , respectively. The resting state time-activity curve is presented in F (). Values are expressed as means ± S.D. The number of subjects who took part in the exercise studies was 14, while 7 were tested while resting. * P < 0.05 vs. baseline; † P < 0.05 and ††P < 0.01 vs. 30 % intensity, and ‡ P < 0.01 vs. 55 % intensity.

Circulating tracer concentrations

As shown in Fig. 3F, after injection of [¹⁸F]FDG, plasma radioactivity increased immediately but then started to decrease rapidly within a few minutes, and was very low 25 min after the tracer injection and exercise. The availability of the tracer (the area under the time-activity curves; AUC) calculated from the plasma time-activity curves was significantly larger in the resting subjects, but was similar between the different exercise intensity levels (data not shown). The AUC between the end of exercise and the start of the cardiac imaging was approximately 21 % of the total AUC. In addition, the variability of the AUC during this period between the different exercise intensities was less than 2 % of the total AUC.

Myocardial glucose uptake

Myocardial glucose uptake did not increase in a linear manner with increasing exercise intensity. Compared to the resting state, exercise doubled myocardial glucose uptake at 30 % (P = 0.056) and 55 % _O2,max (P < 0.05, Fig. 4A). At the highest exercise intensity, glucose uptake decreased significantly as compared to both the 30 % and 55 % intensity levels (P < 0.05), but remained somewhat higher as compared to the resting state. However, the difference between the highest exercise intensity and the resting state was not statistically significant (P = 0.18). Serum FFA concentration at the end of exercise and myocardial glucose uptake correlated inversely at rest (Fig. 5A) and during low-intensity exercise (Fig. 5B). However, during moderate- and high-intensity exercise (Fig. 5C and D), no significant association between serum FFA and myocardial glucose uptake was found. Plasma lactate concentration at the end of exercise was significantly associated with myocardial glucose uptake only during the 55 % intensity level (r = -0.56, P < 0.05, Fig. 6C), but not any more when the outlier point was removed (r = -0.26, P = not significant). Serum insulin concentrations were not significantly associated with myocardial glucose uptake (data not shown).

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Figure 4. Myocardial (A) and quadriceps femoris muscle (B) glucose uptake during rest and exercise (30, 55 and 75 % O2,max) Glucose uptake is shown per unit of mass. Values are expressed as means ± S.D. The number of subjects who took part in the exercise study was 14, while the number of subjects tested while resting was 7 in A and 12 in B. * P < 0.01 compared with 30 and 55 % O2,max intensity; **P < 0.01 compared with 30 % O2,max intensity.

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Figure 5. Association between myocardial glucose uptake and serum FFA concentration at rest (A), and while exercising at 30 % (B), 55 % (C) and 75 % O2,max (D)

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Figure 6. Association between myocardial glucose uptake and plasma lactate concentration at rest (A), and while exercising at 30 % (B), 55 % (C) and 75 % O2,max (D)

Skeletal muscle glucose uptake

QF glucose uptake paralleled the increase in exercise intensity from rest to 30 % and then 55 % _O2,max (P < 0.001; Fig. 4B). Glucose uptake tended to increase further at the intensity of 75 % _O2,max (P = 0.065). There was no correlation between skeletal muscle glucose uptake and plasma lactate, serum FFA or insulin either at rest or during the three different exercise intensities (data not shown). Example myocardial and skeletal muscle PET images with ROIs are shown in Fig. 2.

	DISCUSSION

Top Abstract Introduction Methods Results Discussion References

The purpose of this study was to investigate the effect of exercise on myocardial glucose uptake and whether this glucose uptake pattern is similar in skeletal muscle. We found that in contrast to skeletal muscle, myocardial glucose uptake did not increase linearly with increasing exercise intensity. During low- and moderate-intensity exercise, myocardial glucose uptake doubled as compared to the resting state, but during the highest intensity it was lower than during the other exercise levels. This indicates that during high-intensity exercise the increased myocardial energy requirements are provided by substrates other than glucose. At rest and during low-intensity exercise, myocardial glucose uptake correlated inversely with circulating levels of FFAs, indicating that the glucose-FFA cycle operates under these conditions. However, during higher exercise intensities, this association disappeared. In contrast to the myocardial responses, skeletal muscle glucose uptake rose in parallel with exercise intensity, a result that is in accordance with those of previous studies (Kjaer et al. 1986; Kristiansen et al. 2000; van Loon et al. 2001).

There is a paucity of data in the literature regarding myocardial glucose uptake during exercise. There are only two previous studies in which myocardial glucose uptake was quantified during exercise or myocardial stress (Gertz et al. 1988; Camici et al. 1989). Gertz et al. (1988) found in a dual-carbon-labelled isotope study that myocardial glucose uptake doubled during exercise at 40 % _O2,max compared to the resting state, which is concordant with the results of the present study. According to our results, increasing the exercise intensity (to 55 % _O2,max) did not further enhance glucose uptake. Interestingly, high-intensity exercise (75 % _O2,max) led to a significant decrease in myocardial glucose uptake when lactate levels increased almost 10-fold. In contrast, in a study by Camici et al. (1989), cardiac pacing evoked no increase in lactate levels, while myocardial glucose uptake increased in parallel with heart rate. Because lactate is one of the main energy substrates utilised during exercise and its concentration may increase over 10 times during strenuous exercise (Kjaer et al. 1986), the dynamics of myocardial glucose uptake during cardiac pacing does not represent physiological conditions.

FFAs play an important role in determining the rate of myocardial glucose uptake through the glucose-fatty acid cycle both at rest (Wisneski et al. 1985, 1990; Nuutila et al. 1992) and during prolonged low- to moderate-intensity exercise (Wahlqvist et al. 1973), but this seems to be unlikely during high-intensity exercise. In our study, myocardial glucose uptake was inversely associated with the circulating levels of FFAs at rest and during low-intensity exercise, which is concordant with the findings by Wahlqvist et al. (1973). However, this negative relationship was not seen during exercise at higher intensities (55 and 75 % _O2,max) in our study. Bertrand et al. (1977) hypothesised that glucose and lactate would compensate for the decrease in FFA availability as an energy source during exercise. Evidence from animal studies suggests that an enhanced supply of lactate could effectively inhibit cardiac fatty acid oxidation (Spitzer, 1974; Drake et al. 1980; Bielefeld et al. 1985) by inhibiting the activity of carnityl acyl CoA transferase in the cardiac myocyte (Bielefeld et al. 1985).

Since serum FFA concentration changes were minor during exercise, increased lactate availability and uptake could provide an explanation as to why myocardial glucose uptake was not further increased at the highest exercise intensity. It has been shown that myocardial lactate extraction is related to arterial lactate levels at rest (Gertz et al. 1980) and during submaximal exercise (Carlsten et al. 1961; Krasnow et al. 1962). It has been suggested that lactate could account for up to 65 % of the substrate for myocardial oxidative metabolism during exercise (Keul, 1971; Bertrand et al. 1977). Takala et al. (1983) showed in a study using rats that myocardial glucose uptake was decreased during 20 min of swimming exercise when lactate levels increased sevenfold, suggesting that inhibition of myocardial glucose uptake during exercise is due to an increased availability of other substrates for oxidative metabolism.

An enhanced availability of lactate due to increased exercise intensity provides an alternative energy source for the myocardium, therefore diminishing the demand for glucose. This may serve as a cardioprotective mechanism during ischaemic stress as well as during conditions of increased cardiac work, since lactate has been shown to divert glucose from glycolysis to glycogen synthesis, causing accumulation of glycogen in myocardial cells (Depre et al. 1993, 1998). The lack of inverse association with serum lactate and myocardial glucose uptake during high-intensity exercise might be due to the inability of PET and [¹⁸F]FDG to measure separately the amount of glucose entering oxidative and non-oxidative metabolism. Using [¹⁸F]FDG it is possible to measure glucose uptake, but not to obtain direct information of its later fate. Nevertheless, it may be hypothesised that by increasing the exercise intensity and lactate availability the proportion of glucose entering glycolysis will diminish, whereas the proportion entering glycogen synthesis increases (Depre et al. 1993).

In contrast to the myocardial responses, skeletal muscle glucose uptake rose in parallel with exercise intensity in the present study, suggesting that skeletal muscle is more dependent upon a continuous glucose supply during high-intensity exercise. At rest and during low- to moderate-intensity exercise, lipids predominate as the preferred energy source. When exercise intensity increases, a shift in substrate utilisation towards carbohydrates occurs (Brooks & Mercier, 1994; Friedlander et al. 1997).

Limitations of the study

Except for insulin and cortisol, other hormonal factors were not measured in the present study. Therefore, we cannot exclude the influence of other factors such as growth hormone or cathecolamines on glucose uptake. However, myocardial glucose extraction has not been significantly related to arterial insulin, growth hormone or glucocorticoid concentrations during exercise (Wahlqvist et al. 1973). Observed responses in myocardial and skeletal muscle glucose uptake may be partly related to hormonal changes. In the present study, cortisol levels increased in parallel with exercise intensity. However, neither insulin nor cortisol concentrations were correlated with myocardial glucose uptake levels during exercise (data not shown). During exercise at the highest intensity, plasma glucose increased slightly, but the average glucose value remained euglycaemic.

Currently, PET scanning during dynamic exercise is technically problematic. Therefore, the injection of [¹⁸F]FDG, as utilised in the present study, was performed during exercise, which was then continued for an additional 25 min, and scanning was performed directly after the exercise. Despite this, the measured glucose uptake values reflect the actual glucose uptake during exercise. After phosphorylation, the glucose analogue ([¹⁸F]FDG) is trapped inside the muscle cell where further metabolism is prevented due to its chemical characteristics. This metabolic state of phosphorylated [¹⁸F]FDG is preserved for approximately 2 h after injection (Gallagher et al. 1977). Plasma radioactivity peaked shortly after [¹⁸F]FDG injection, and then decreased quickly during exercise (Fig. 3F). In addition to the tissue glucose uptake, the total uptake of tracer into the tissues is dependent upon the availability of the tracer, specifically the AUC for the time-activity relationship. The AUC between the end of exercise and the start of the cardiac imaging was only a fraction of the total AUC, and the variability of AUC during this period between the different exercise intensities was very small (< 2 % of the total AUC). Furthermore, taking into account that during this period tissue glucose uptake is presumably lower than during exercise, the contribution of the post-exercise period of 12 min to the results of the present study is insignificant. Moreover, our results obtained at the 30 and 55 % _O2,max intensity levels are in accordance with a study conducted by Gertz et al. (1988), although they used a different approach.

As mentioned earlier, [¹⁸F]FDG enables us to quantify tissue glucose uptake but provides no information about the fate of glucose in the cell. Thus, we were unable to measure the amount of glucose entering oxidative and non-oxidative metabolism. The affinity of [¹⁸F]FDG and glucose for glucose transporters and hexokinase are not necessarily always identical. These differences are corrected by using a correction factor, the LC. In experimental animal studies of anoxia, the physiological range of flow, insulin, glucose and external work did not effect LC (Ratib et al. 1982; Marshall et al. 1983; Huang et al. 1987; Krivokapich et al. 1987). In contrast, in some studies changes in the sensitivity of LC to supraphysiological amounts of lactate (40 mM: Hariharan et al. 1995), insulin and glucose (Ng et al. 1991) were documented. All of these studies were performed with isolated heart preparations under non-physiological or in vitro conditions. Currently, there is only one study in humans where the myocardial LC was tested, and it was shown to be stable under basal and insulin-stimulated conditions (Ng et al. 1998).

In order to limit the radioactive dosage, two groups of volunteers were studied; one at rest and the other directly after exercise.

In conclusion, the results of the present study demonstrate that exercise increases myocardial glucose uptake, but that this increase does not parallel exercise intensity, in contrast to the situation in skeletal muscle. These findings suggest that the increased myocardial energy that is needed during high-intensity exercise is supplied by substrates other than glucose.

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Acknowledgements

The authors thank the entire staff of the PET Centre and Jukka Kapanen, Paavo Nurmi Center, for _O2,max determinations. This work was supported by grants from the Novo Nordisk foundation, the Finnish Foundation for Cardiovascular Research, the Turku University Foundation and the University Hospital of Turku.

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