Vol. 88, Issue 6, 1949-1954, June 2000
Simultaneous NMR microdialysis study of brain glucose
metabolism in relation to fasting or exercise in the rat
F.
Béquet,
M.
Pérès,
D.
Gomez-Mérino,
M.
Berthelot,
P.
Satabin,
C.
Piérard, and
C. Y.
Guezennec
Department of Physiology, Institut de Médecine
Aérospatiale du Service de Santé des Armées,
91223 Brétigny-sur-Orge, France
 |
ABSTRACT |
To study the impact of exercise or fasting and of
subsequent glucose supplementation on glucose metabolism in rats, a
spectrophotometric method was used to determine peripheral blood
glucose; a technique associating 1H-NMR spectroscopy and
cortical microdialysis was also used to observe intra- plus
extracellular and extracellular brain glucose variations,
respectively. Compared with control animals (204 ± 19 µM in dialysate, n = 10), exercise increased brain
extracellular glucose levels to 274 ± 22 µM (n = 8; P < 0.05), whereas fasting induced a drop in glucose
levels down to 140 ± 9 µM (n = 8; P < 0.05).
After fasting, glucose supplemented by infusion increased glycemia from
7.4 ± 0.4 to 19.9 ± 0.8 mM (n = 10; P < 0.001), as well as extracellular and extra- plus intracellular brain glucose to
263 ± 20% (n = 8; P < 0.001) and 342 ± 28%
(n = 8; P < 0.001), respectively, over basal for that
group. After exercise, a similar infusion increased glycemia from 7.3 ± 0.3 to 16.8 ± 1.1 mM (n = 10; P < 0.001), as
well as extracellular and extra- plus intracellular brain glucose to
178 ± 19% (n = 8; P < 0.001) and 244 ± 20%
(n = 8; P < 0.001), respectively, over basal for that
group. These results confirmed the existence of a link between glucose
level variations in peripheral and cerebral areas but also showed that exercise increased extracellular brain glucose levels despite peripheral hypoglycemia, suggesting a specific regulation mechanism of
cerebral glucose metabolism during exercise.
nuclear magnetic resonance spectroscopy
| |
INTRODUCTION |
SOME STUDIES ON MUSCULAR FATIGUE have shown that
glucose supplementation can delay fatigue induced by physical exercise
or pointed out that supplementing carbohydrates during exercise
significantly lengthened its duration (10, 13, 19).
Early research by Levine et al. (26) in the 1920's established the
link between hypoglycemia and extreme fatigue. Later, work performed in
Scandinavia (6, 34) revealed the existence of a link between fatigue
and peripheral glycogen utilization. However, all fatigue-related
phenomena cannot be explained by this sole observation. In 1983, Coyle
et al. (11) showed that, in many cases, ingested glucose cannot
diminish glycogen utilization during exercise. Experiments were carried
out by Koslowski et al. (25) in 1981 in dogs in which glucose was
directly infused in the carotid artery. Results showed that supplying
glucose to the brain could delay fatigue, pointing on an action of
glucose supplementation on central fatigue.
Mechanisms and kinetics of glucose transport across the blood-brain
barrier (BBB) and inside the brain are well known (12, 18, 27). They
involve glucose transporters of the GLUT family; GLUT-1 is exclusively
involved along the BBB, whereas, inside the brain, transporters are
mainly GLUT-1 and GLUT-3, both on neural cell membranes (9, 14, 20,
38). However, an interesting question remains concerning glucose
regulation and transport between the peripheral compartment and brain
extra- and intracellular compartments in some physiological situations,
such as physical exercise and fasting.
In this study, we first focused on the relationship between glycemic
variations and cerebral glucose variations after exercise and fasting,
where glucose deficits could influence several central regulations.
Then we studied the influence of a subsequent glucose supplementation.
We aimed, first, at determining whether or not exercise could
specifically modify cerebral glucose regulation, compared with fasting,
and, second, at determining to what extent postexercise glucose
supplementation could influence this regulation process. To this end,
we used an original technique developed in our laboratory (32),
associating brain microdialysis to determine glucose concentrations in
the extracellular compartment (5) and NMR spectroscopy to monitor
extra- and intracellular compartments in the brain (4, 15).
| |
MATERIALS AND METHODS |
Animals.
Male Wistar rats weighing 250-300 g from Janvier (Le
Genest-Saint-Isle, France) were used in this experiment. They were
individually housed in a temperature-controlled room (20 ± 1°C)
illuminated from 8:00 AM to 8:00 PM. Food and water were available ad
libitum (except during the food-deprivation experiment).
Surgery.
Eight to ten days before the experiment, the animals were anesthetized
with ketamine chlorydrate (150 mg/kg ip) and then placed in a
stereotaxic frame (DKI model 900). Head skin was incised, temporal
muscles were retracted on both sides of the head, and the cranium was
cleaned of all organic material with a hydrogen peroxide solution. A
1-mm-diameter hole was drilled in the parietal bone, and a
microdialysis stainless guide probe (Carnegie Medicin, Stockholm,
Sweden) was placed horizontally in the frontoparietal cortex, after
removal of dura matter, and sealed with dental cement. The coordinates
used, according to the Paxinos and Watson atlas (30), were 2.6 mm
behind the bregma and 1.5 mm below the horizontal zero plane. A
triangular head-holding device was then chronically implanted to house
the NMR coil and to allow the head to be attached to the NMR probe.
This system and the microdialysis guide were covered by a polyethylene protection.
On the day of the experiment, the animals were anesthetized with 0.5%
halothane (Belamont, Paris, France), tracheotomized, immobilized with
0.1 mg · kg
1 · h1
of d-tubocurarine (Sigma Chemical, St. Louis, MO), and
artificially ventilated with a mixture of 30% O2 and 70%
N2O. After the dialysis probe was introduced, the femoral
artery and vein were catheterized for blood sample collection and to
infuse glucose, respectively. In the treadmill situation (before and
just after running), blood was sampled from the tail vein.
Physiological monitoring.
The femoral artery catheter was used to monitor mean arterial blood
pressure, PO2,
PCO2, and pH. Respiratory rate and
volume were adjusted (volume = 2.5 ml; frequency = 70 counts/min) to
keep arterial pH at 7.35 ± 0.05, PCO2 at 38 ± 3 Torr, and
PO2 at 108 ± 3 Torr.
The electrocardiogram was monitored, and body temperature was
maintained close to 38 ± 0.5°C throughout the experiment.
Microdialysis procedure.
The microdialysis membrane was 4 mm long, with a 500-µM diameter and
a molecular cutoff weight of 20 (CMA 20 microdialysis probe model,
Carnegie Medicin). In vitro calibration tests completed before each experiment showed a relative recovery of ~14% for glucose.
The infusion was performed with an artificial cerebrospinal fluid (CSF)
containing (in mM) 119.5 NaCl, 4.75 KCl, 1.27 CaCl2, 1.19 KH2PO4, 1.19 MgSO4, and 1.6 Na2HPO4. The flow rate (2.0 µl/min) obtained
with the CMA 102 pump (Carnegie Medicin) allowed for the collection
every 30 min of 60-µl samples, which were stored in refrigerated microvials.
Dialysates analysis.
The dialysates were analyzed by reverse-phase HPLC with fluorometric
detection. The system consisted of a 10-µl sample loop leading to an
Eco-Cart Lichrospher RP-18 (5-µm) column. The mobile phase consisted
of a 0.2 M Tris buffer (pH = 8) with EDTA. The enzymatic reagent was a
hexokinase plus glucose-6-phosphate dehydrogenase combination.
Detection was done at a 260-nm excitation wavelength and a 460-nm
emission wavelength with a Jasco FP-920 fluorometric detector.
NMR spectroscopy.
NMR experiments were carried out by using an AM 400 Wide Bore Bruker
spectrometer (Oxford Instruments) equipped with a 9.4-T, 89-mm-bore
vertical magnet and a custom-made probe for in vivo studies. A one-turn
elliptical surface radio-frequency coil (11 × 8 mm) was used to
acquire the 1H-NMR signal. Two-dimensional (2D) correlation
spectroscopy (COSY) spectra of glucose and glutamate/glutamine pool
were obtained in module mode by using the SUPERCOSY sequence as
previously described (2, 31). Briefly, the SUPERCOSY pulse scheme had
two spin-echo delays that were introduced symmetrically with respect to
the second 
/2 pulse. The delay might be adjusted for a specific
range of scalar coupling constant J. This delay was set to 86 ms for 2D COSY 1H spectra of small cerebral metabolites. It
corresponded to 2 × 0.3/J, with J = 7 Hz (mean
scalar coupling value of freely rotating rotors in open chains). The
delay also allowed further reduction of the remaining water signal and
suppression of phospholipid and protein signals by T2 filtering. The
quadrature in dimension 1 was obtained by phase modulation.
Taking the T2 relaxation of small metabolites into account, we used 86 ms for the spin-echo time. This delay also enabled a further reduction
of the remaining water signal and the suppression through T2 filtering
of the phospholipid and protein signal. Acquisition of eight free
induction decays in the time domain T2 for each of the 128 increments
in the time domain T1 led to a total acquisition time of 30 min. The
spectral width in the corresponding frequency domain in F1 and F2
dimensions was 10 ppm. Before the 2D Fourier transform, the data were
multiplied by an unshifted sine bell function in the two dimensions and
were zero filled to obtain a 1,024 × 1,024 data point matrix. In
vivo 2D chemical shifts were expressed in comparison to water
resonance, assigned at 4.75 ppm in the two dimensions. Cerebral
metabolite levels were measured on the 2D spectra according to the
volume of their respective cross-correlation peaks by means of a
specific software (Aurelia).
Measuring glycemia.
Glycemia was measured by means of the peroxydase method (glucose
enzymatique color kit, BIOTROL) with a spectrophotometric detection at
500 nm.
Sampling CSF.
A direct sampling of CSF was used to determine the real concentration
of glucose in the extracellular compartment. Sampling was through a
puncture within the third ventricle, thus allowing for 100-µl samples
of CSF, analyzed on line with HPLC (n = 5).
Experimental protocol.
A first group of 10 rats was used to determine the values of glycemia
and extracellular brain glucose in normal feeding and rest conditions.
Then two groups of eight rats were randomized: the first group was
deprived of food for 36 h, and the second was submitted to strenuous
and prolonged exercise on a treadmill (running for 1 h 30 min at 30 m/min, 0% grade) just before the experiment, after 1 wk of training.
Animals underwent the surgical procedure described in Surgery
above after running or fasting, when equilibration of the dialysis
membrane occurs. Dialysates and NMR data were simultaneously obtained
every 30 min, with the first dialysate being sampled after the probe
was equilibrated for 2 h. The protocol for glucose infusion was as
follows: 30% glucose constantly infused for 2 h at a rate of 0.3 ml · h1 · 100 g1. Data acquisition was done postexercise, for 4 h
30 min, with a stable state of 1 h 30 min, a glucose infusion of 2 h,
and then a return to stable state for 1 h. Blood and cerebral glucose
were analyzed after sampling; dialysates were then kept frozen at
80°C for later analysis.
Data analysis.
Data concerning glycemic variations and extracellular glucose level
comparisons are expressed as means ± SE of concentrations. Data
concerning the effect of infusion are expressed as means ± SE of
percent increase or decrease vs. concentrations obtained before
infusion. Percentage was used instead of concentration to allow a
direct comparison of glucose variations in the three compartments.
Basal values of glucose were determined for each rat by using the
dialysates collected before the infusion. A one-way ANOVA was performed
on the basal values of glucose for the two situations of fasting and
exercise, to determine whether basal levels differed significantly. The
effect of infusion on glucose level in the two situations was assessed
by repeated-measures ANOVA. Analyses also included a two-way ANOVA for
repeated measures (situation × time) to directly compare the
glucose level in the two different situations. Post hoc analyses were
performed by using Newman-Keuls.
Significance was accepted at P < 0.05.
| |
RESULTS |
Effect of food deprivation, exercise, and glucose infusion on blood
glucose metabolism.
A mean value for glycemia in appropriate feeding and rest conditions
was obtained from the group of rats kept under these conditions. This
value was 10.07 ± 0.24 mM under anesthesia (n = 10). This
group of rats was used as a control group throughout the study.
Food deprivation and strenuous exercise both induced hypoglycemia;
concentrations were 6.9 ± 0.3 mM after fasting (n = 10) and
7.1 ± 0.2 mM after exercise (n = 10), results which
are significantly different from those of the control group (P < 0.001).
Glucose infusion was expected to induce a significant hyperglycemia.
The results show a progressive increase in glycemia during 90 min of
infusion, reaching a maximum of 19.9 ± 0.8 mM after fasting and 16.8 ± 1.1 mM after running (P < 0.001). Once the infusion was
complete, glycemia decreased to a level close to the normoglycemic
values but significantly higher than the control value: 11.7 ± 0.7 mM
after fasting (P < 0.05) and 12.8 ± 1.1 mM after running
(P < 0.01) (Fig. 1).
View larger version (17K):
[in this window]
[in a new window]
|
Fig. 1.
Variations in venous blood glycemia after fasting (n = 10 rats)
and exercise (n = 10 rats) with glucose infusion between 0 and
120 min, compared with normoglycemic (N) value. * P < 0.05, ** P < 0.01, *** P < 0.001, compared
with N value.
|
|
Effect of hypoglycemia induced by food deprivation and exercise on
cerebral glucose metabolism.
Figure 2 shows the glucose concentration in
brain microdialysates for the two hypoglycemic situations vs. the
normoglycemic one. Cerebral glucose decreased in line with the drop in
glycemia after food deprivation (139.5 ± 9.1 µM; n = 8) but
showed an unexpected high level after the treadmill workout (273.6 ± 22.1 µM; n = 8), compared with the normoglycemic situation
(203.9 ± 18.7 µM; n = 10) (P < 0.05).
View larger version (16K):
[in this window]
[in a new window]
|
Fig. 2.
Glucose concentration in dialysates before glucose infusion in
situation of fasting-induced hypoglycemia (after fasting; n = 8 rats) or exercise-induced hypoglycemia (after exercise; n = 8 rats), compared with control (n = 10 rats). * P < 0.05 compared with control; ### P < 0.001, after fasting vs. after exercise.
|
|
Effect of glucose infusion on cerebral glucose metabolism.
In fasting conditions, brain glucose levels increased during infusion,
in line with variations in glycemia, and reached a maximum of 342 ± 28% for total brain glucose, as detected by NMR, and 263 ± 20% for
extracellular brain glucose, as noted by microdialysis (P < 0.001), compared with baseline. A decrease was then observed during all
postinfusion periods in both compartments (Fig.
3A).
View larger version (34K):
[in this window]
[in a new window]
|
Fig. 3.
Percent variations in glucose in the 2 brain compartments, compared
with variations in glycemia (in mM) after fasting (n = 8 rats;
A) and after exercise (n = 8 rats; B). Glucose
infusion was between 0 and 120 min. C, control. * P < 0.05, ** P < 0.01, *** P < 0.001, compared
with 0 time point.
|
|
Under conditions of physical exercise, the increase in cerebral glucose
shifted to the right, compared with glycemic variations, and was not
significant before 30 min of infusion. The increase was smaller in
exercise than in fasting and reached a maximum of 244 ± 20% for NMR
and 178 ± 19% for microdialysis (P < 0.001), compared with
baseline (Fig. 3B).
It was possible to approximate the percentage of glucose increase in
the intracellular compartment from the mean basal concentration values
already known for extra- and intracellular compartments: CSF puncture
showed a concentration of 4 mM in the extracellular compartment, and
the concentration is known to be around ~1 mM inside neuronal cells
(3). With the use of this data, together with the progression factor
given by NMR spectroscopy and microdialysis during infusion, it was
possible to calculate the increase factor for the intracellular
compartment as follows
where
I is concentration of glucose inside cells; E is concentration of
glucose in the extracellular compartment; T is concentration of glucose
in both compartments; x is maximum factor of increase under perfusion;
p is after perfusion; and 0 is basal.
In the case of fasting, data were
resulting
in a glucose increase in the intracellular compartment of approximately
i.e.,
a 660% increase.
In the case of exercise, data were
resulting
in a glucose increase in the intracellular compartment of approximately
i.e.,
a 480% increase.
By comparing these results to those observed in microdialysis, which
were 263 ± 20% for fasting and 178 ± 19% for exercise, the
increase during infusion in the intracellular compartment was found to
be ~2.5 times greater than in the extracellular compartment in both
situations (660%/260% 
2.5 and 480%/180% 2.6).
| |
DISCUSSION |
Glucose infused after strenuous physical exercise or fasting resulted
in significant hyperglycemia. However, the glucose increase was
slightly greater after food deprivation than after exercise. This can
be explained by an enhanced muscle glucose transfer across muscle
membrane, as previously demonstrated (24, 33), caused by the phenomenon
of nonsuppressive insulin-like activity and by enhanced sensitivity to
insulin during and after exercise. This result highlights a metabolic
difference existing between exercise and fasting in terms of peripheral
glucose regulation.
Some studies have previously described how glucose is transferred
between blood and brain (12, 27), but the data presented here focus on
the difference between blood and brain glucose metabolism after fasting
and physical exercise. Results confirmed the existence of a direct link
between glycemia variations and cerebral glucose concentrations. This
means that, under such physiological conditions of glycemia, there is
no limitation in glucose transport between the peripheral compartment
and the brain across the BBB (18). During infusion, extra- and
intracellular cerebral glucose increased more significantly in
conditions of fasting than in conditions of exercise. Long-term
regulation mechanisms might come into play: evidence was found that the
number of GLUT-1 glucose transporters on the BBB (7) and of GLUT-3
transporters on the neuron membrane (36) were inversely proportional to
blood glucose concentration. A 36-h fast would cause an increase in the
quantity of GLUT-1 transporters on the BBB (7), contrary to what 1 h 30 min of running would do, where hypoglycemia is very brief. Kinetic
data, which show faster cerebral glucose increases in the food
deprivation situation, strongly support this hypothesis.
Coupling NMR spectroscopy with microdialysis allowed for the separation
of data pertaining to intra- and extracellular compartments. Indeed,
NMR addresses mainly both compartments, as the microvascular compartment represents a very slight percentage of the NMR volume and
can be ignored and microdialysis only addresses the extracellular compartment. The data showed a greater increase inside
cells, ~2.5 times the increase in CSF, as calculated above. This
confirms that, when the cerebral glucose concentration increases,
neurons are privileged compared with the rest of the brain. This, in
turn, is due to the characteristic differences between GLUT-1 and
GLUT-3, the latter being in charge of transferring glucose across the neuron membrane. As a matter of fact, the Michaelis-Menten constant of
GLUT-3 is three times smaller than that of GLUT-1; therefore, when
glucose increases in blood, it crosses the BBB by the exclusive means
of GLUT-1 and is then redirected toward nervous system
cells. The transfer across the BBB was noted as more
important in the case of fasting. However, figures seemed to not be
significant for cell membrane crossing. This tends to show that the
long-term transporter regulation obtained for GLUT-1 does not apply to
GLUT-3 in our fasting protocol, unlike results obtained in a previous study on the effect of chronic hypoglycemia on GLUT-3 (36). In other
words, it seems that a slight and long-enough hypoglycemia is
sufficient to induce GLUT-1 protein in rat brain neurons but not GLUT-3
protein. Our study did not entail the measure of GLUT transporters, but
the way they operate was reflected and thus observed by the differences
in glucose content in the two brain compartments during infusion. These
results all seem to indicate that the effects of peripheral
hyperglycemia are regulated in the brain by the glucose transport
system across the BBB and the cell membranes, involving the
transporters of the GLUT family. Despite previous observations of a
speedy effect of glucose supplementation on the parameters of physical
exercise (29), the results presented herein evidence a latency between
the start of glucose infusion and the increase in cerebral glucose
levels. However, our glucose supplementation occurred only after
exercise, and the situation could be different when supplementation
occurs before or during exercise.
Our most unexpected results involved brain glucose regulation in
hypoglycemic situations. A decrease in brain glucose levels was
expected in the two experimental conditions, but the extracellular concentrations noted after exercise were far more superior than those
observed in the normoglycemic state or after fasting. Two main
hypotheses may account for these results. First, exercise is known to
require a reorganization of the vasodilatation/vasoconstriction system
and an increase in heart beat rate, leading to a significant increase
in cerebral blood flow (21, 23). This might explain the increase in
cerebral glucose levels despite the peripheral decrease. Second,
exercise is known to induce a significant rise in glucocorticoids,
which are strongly involved in cerebral glycogen catabolism in brain
astrocytes (17, 30). Exercise is likely to activate this metabolic
cascade, thereby increasing the quantity of extracellular glucose.
Moreover, fasting decreases glucocorticoid levels (22), and the
differences observed between exercise and fasting results may be
enhanced by these metabolic variations. Both hypotheses may partly
explain the phenomenon, which could be a mechanism protecting brain
tissue during exercise and/or the reflection of an induced central
fatigue expressed through a link with some neurotransmitters.
Hypoglycemia is known to be a peripheral fatigue marker, reflecting the
major role of glucose metabolism in physical performance. The results
presented herein show that cerebral glucose could be a central fatigue
index as well, probably related to another central intermediary such as
serotonin (8, 37), GABA (1), or another neurotransmitter more directly
involved than glucose in the appearance of fatigue.
| |
FOOTNOTES |
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. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: F. Béquet,
IMASSA-B.P. 73, 91223 Brétigny-sur-Orge Cedex, France
(E-mail: fbequet{at}club-internet.fr).
Received 19 March 1999; accepted in final form 19 January 2000.
| |
REFERENCES |
1.
Abdelmalki, A,
Merino D,
Bonneau D,
Bigard AX,
and
Guezennec CY.
Administration of a GABAB agonist baclofen before running to exhaustion in the rat: effect on performance and some indicators of fatigue.
Int J Sports Med
18:
75-78,
1997[ISI][Medline].
2.
Barrère, B,
Pérès M,
Gillet B,
Mergui S,
Beloeil JC,
and
Seylaz J.
2D COSY 1H NMR: a new tool for studying in situ brain metabolism in the living animal.
FEBS Lett
264:
198-202,
1990[Medline].
3.
Behar, KL,
Petroff OA,
Prichard JW,
Alger JR,
and
Shulman RG.
Detection of metabolites in rabbit brain by 13C NMR spectroscopy following administration of [1-13C]glucose.
Magn Reson Med
3:
911-920,
1986[ISI][Medline].
4.
Bendall, MR.
Calibrated uncoupling of tightly coupled concentric surface coils for in vivo NMR.
Magn Reson Med
8:
380-393,
1988[Medline].
5.
Benveniste, H,
and
Diemer NH.
Cellular reactions to implantation of microdialysis tube in the rat hippocampus.
Acta Neuropathol (Berl)
74:
234-238,
1988.
6.
Bergström, J,
and
Hultman E.
A study of glycogen metabolism during exercise in man.
Scand J Clin Lab Invest
19:
218-228,
1967[ISI][Medline].
7.
Boado, RJ,
and
Pardridge WM.
Glucose deprivation causes posttranscriptional enhancement of brain capillary endothelial glucose transporter gene expression via GLUT1 mRNA stabilization.
J Neurochem
60:
2290-2296,
1993[ISI][Medline].
8.
Chaouloff, F.
Effect of physical exercise on central serotoninergic systems.
Med Sci Sports Exerc
29:
58-62,
1997[ISI][Medline].
9.
Cornford, EM,
Hyman S,
and
Swartz BE.
The human brain GLUT1 glucose transporter: ultrastructural localization to the blood-brain barrier endothelia.
J Cereb Blood Flow Metab
14:
106-112,
1994[Medline].
10.
Coyle, EF,
Coggan AR,
Hemmert MK,
and
Ivy JL.
Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrates.
J Appl Physiol
61:
165-172,
1986[Abstract/Free Full Text].
11.
Coyle, EF,
Hagberg JM,
Hurley BF,
Martin WH,
Ehsan AA,
and
Holloszy JO.
Carbohydrate feeding during prolonged strenuous exercise can delay fatigue.
J Appl Physiol
55:
230-235,
1983[Abstract/Free Full Text].
12.
Crone, C.
Facilitated transfer of glucose from blood into brain tissue.
J Physiol (Lond)
185:
103-113,
1965.
13.
Danguir, J.
Internal milieu and sleep homeostasis.
In: Sleep Peptides: Basic and Chemical Approaches, edited by Inove S,
and Schneider-Helmert D.. Tokyo, Japan: Science Society Press, 1988, p. 53-72.
14.
Dick, APK,
and
Harik SI.
Distribution of the glucose transporter in the mammalian brain.
J Neurochem
46:
1406-1411,
1986[Medline].
15.
Evelhoch, JL,
Crowley MG,
and
Ackerman JJH
Signal-to-noise optimisation and observed volume localization with circular surface coils.
J Magn Reson
56:
110-124,
1984.
16.
Forsyth, RJ.
Astrocytes and the delivery of glucose from plasma to neuron.
Neurochem Int
28:
231-241,
1996[ISI][Medline].
17.
Goldberg, ND,
and
O'Toole AG.
The properties of glycogen synthetase and regulation of glycogen biosynthesis in rat brain.
J Biol Chem
244:
3053-3061,
1969[Abstract/Free Full Text].
18.
Gruetter, R,
Ugurbil K,
and
Seaquist ER.
Steady-state cerebral glucose concentrations and transport in the human brain.
J Neurochem
70:
397-408,
1998[ISI][Medline].
19.
Guezennec, CY.
Oxidation rates, complex carbohydrates, and exercise. Practical recommendations.
Sports Med
19:
365-372,
1995[Medline].
20.
Haber, RS,
Weinstein SP,
O'Boyle E,
and
Morgello S.
Tissue distribution of the human GLUT3 glucose transporter.
Endocrinology
132:
2538-2543,
1993[Abstract].
21.
Hellstrom, G,
Fischer-Colbrie W,
Wahlgren NG,
and
Jogestrand T.
Carotid artery blood flow and middle cerebral artery blood flow velocity during physical exercise.
J Appl Physiol
81:
413-418,
1996[Abstract/Free Full Text].
22.
Hendrikx, A.
Aspects of Steroid Metabolism in Obese Subjects Under Various Nutritional Conditions. Brussels: Arscia Vitgaven, 1968.
23.
Herholz, K,
Buskies W,
Rist M,
Pawlik G,
Hollmann W,
and
Heiss WD.
Regional cerebral blood flow in man at rest and during exercise.
J Neurol
234:
9-13,
1987[ISI][Medline].
24.
Ivy, JL,
Frishberg BA,
Farrell SW,
Miller WJ,
and
Sherman WM.
Effects of elevated and exercise-reduced muscle glycogen levels on insulin sensitivity.
J Appl Physiol
59:
154-159,
1985[Abstract/Free Full Text].
25.
Koslowski, S,
Brzezinska Z,
Nazar K,
and
Turlejska E.
Carbohydrate availability for the brain and muscle as a factor modifying sympathetic activity during exercise in dogs.
In: Biochemistry of Exercise, edited by Poortmans J,
and Niset G.. Baltimore, MD: Univ Park Press, 1981, chapt. IV B, p. 54-62.
26.
Levine, SA,
Gordon B,
and
Derick CL.
Some changes in the chemical constituents of the blood following a marathon race.
JAMA
82:
1778-1779,
1924.
27.
Lund-Andersen, H.
Transport of glucose from blood to brain.
Physiol Rev
59:
305-351,
1979[Free Full Text].
28.
Magistretti, PJ.
Regulation of glycogenolysis by neurotransmitters in the central nervous system.
Diabetes Metab
14:
237-246,
1988.
29.
Neufer, PD,
Costill DL,
and
Flynn MG.
Improvements in exercise performance: effects of carbohydrate feeding and diet.
J Appl Physiol
62:
983-988,
1987[Abstract/Free Full Text].
30.
Paxinos, G,
and
Watson C.
The Rat Brain in Stereotaxic Coordinates. New York: Academic, 1982.
31.
Pérès, M,
Fedeli O,
Barrère B,
Gillet B,
Bérenger G,
Seylaz J,
and
Beloeil JC.
In vivo identification and monitoring of changes in rat brain glucose by two-dimensional shift correlated 1H-NMR spectroscopy.
Magn Reson Med
27:
356-361,
1992[Medline].
32.
Piérard, C,
Pérès M,
Guezennec CY,
and
Lagarde D.
Effect of GABA-transaminase inhibition on brain metabolism and aminoacids compartmentation: an in vivo study by 2D 1H NMR spectroscopy coupled with microdialysis.
Exp Brain Res
127:
321-327,
1999[ISI][Medline].
33.
Rodnick, KJ,
Haskell WL,
Swiwlocki ALM,
Foley JE,
and
Reaven GM.
Improved insulin action in muscle, liver, and adipose tissue in physically trained human subjects.
Am J Physiol Endocrinol Metab
253:
E489-E495,
1987[Abstract/Free Full Text].
34.
Saltin, B,
and
Karlsson J.
Muscle glycogen utilization during work of different intensities.
In: Advances in Experimental Medicine and Biology, edited by Pernow B,
and Saltin B.. New York: Plenum, 1971, vol. 11, p. 289-299.
35.
Specter, SE,
Horwitz BA,
and
Beverly JL.
Basal and glucoprivic-induced changes in extracellular GABA in the ventral hypothalamus of Zucker rats.
Am J Physiol Regulatory Integrative Comp Physiol
271:
R388-R392,
1996[Abstract/Free Full Text].
36.
Uehara, Y,
Nipper V,
and
McCall AL.
Chronic insulin hypoglycemia induces GLUT3 protein in rat brain neurons.
Am J Physiol Endocrinol Metab
272:
E716-E719,
1997[Abstract/Free Full Text].
37.
Vahabzadeh, A,
Boutelle MG,
and
Fillenz M.
Effects of changes in rat brain glucose on serotonergic and noradrenergic neurons.
Eur J Neurosci
7:
175-179,
1995[ISI][Medline].
38.
Zeller, K,
Rahner-Welsch S,
and
Kuschinsky W.
Distribution of Glut1 glucose transporters in different brain structures compared with glucose utilization and capillary density of adult rat brains.
J Cereb Blood Flow Metab
17:
204-209,
1997[Medline].
J APPL PHYSIOL 88(6):1949-1954
8570-7587/00 $5.00
Copyright © 2000 the American Physiological Society
TOP
ABSTRACT
INTRODUCTION
