Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.

Abstract

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.

Full text

Page 1

Prior Exercise and Splanchnic Glucose Metabolism

125

J. Clin. Invest.
© The American Society for Clinical Investigation, Inc.
0021-9738/96/07/125/11 $2.00
Volume 98, Number 1, July 1996, 125–135

Effect of Prior Exercise on the Partitioning of an Intestinal Glucose Load between
Splanchnic Bed and Skeletal Muscle

Katherine S. Hamilton, Fiona K. Gibbons, Deanna P. Bracy, D. Brooks Lacy, Alan D. Cherrington, and David H. Wasserman
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232


Abstract

Exercise leads to marked increases in muscle insulin sensi-
tivity and glucose effectiveness. Oral glucose tolerance im-
mediately after exercise is generally not improved. The hy-
pothesis tested by these experiments is that after exercise
the increased muscle glucose uptake during an intestinal
glucose load is counterbalanced by an increase in the effi-
ciency with which glucose enters the circulation and that
this occurs due to an increase in intestinal glucose absorp-
tion or decrease in hepatic glucose disposal. For this pur-
pose, sampling (artery and portal, hepatic, and femoral
veins) and infusion (vena cava, duodenum) catheters and
Doppler flow probes (portal vein, hepatic artery, external il-
iac artery) were implanted 17 d before study. Overnight-
fasted dogs were studied after 150 min of moderate tread-
mill exercise or an equal duration rest period. Glucose
([
C]glucose labeled) was infused in the duodenum at 8 mg/
kg
?
min for 150 min beginning 30 min after exercise or rest
periods. Values, depending on the specific variable, are the
mean
?
SE for six to eight dogs. Measurements are from the
last 60 min of the intraduodenal glucose infusion. In re-
sponse to intraduodenal glucose, arterial plasma glucose
rose more in exercised (103
?
with rested (104
?
2 to 139
?
3 mg/dl) dogs. The greater in-
crease in glucose occurred even though net limb glucose up-
take was elevated after exercise (35
net splanchnic glucose output (5.1
min) and systemic appearance of intraduodenal glucose
(8.1
?
0.6 vs. 6.3
?
0.7 mg/kg
?
min) were also increased due
to a higher net gut glucose output (6.1
kg
?
min). Adaptations at the muscle led to increased net
glycogen deposition after exercise [1.4
(gram of tissue
?
150 min)], while no such increase in glyco-
gen storage was seen in liver [3.9
of tissue
?
150 min) in exercised and sedentary animals, re-
spectively]. These experiments show that the increase in the
ability of previously working muscle to store glycogen is not
solely a result of changes at the muscle itself, but is also a re-
sult of changes in the splanchnic bed that increase the effi-

14







4 to 154

?

6 mg/dl) compared





?
?

5 vs. 20
0.8 vs. 2.1

?

2 mg/min) as
?
0.6 mg/kg





?








?

0.7 vs. 3.6

?

0.9 mg/



?

0.3 vs. 0.5

?

0.1 mg/



?

1.0 vs. 4.1

?

1.1 mg/(gram


ciency with which oral glucose is made available in the sys-
temic circulation. (
J. Clin. Invest.
words: exertion
•
gut
•
liver
•
skeletal muscle
bohydrate


1996. 98:125–135.) Key
•
glucose









•

car-

Introduction

Despite the adaptations that facilitate muscle glucose disposal
after acute exercise, the increase in systemic blood glucose that
occurs in response to oral glucose is generally no less (1–3) and
may even be greater than the response in sedentary subjects
(4, 5). This suggests that prior exercise leads to extramuscular
adaptations that increase glucose availability to peripheral tis-
sues during an oral glucose load. Since the rate of glucose en-
try into the systemic circulation after feeding is determined by
gastrointestinal glucose absorption and net hepatic glucose
balance, it is likely that one or both of these processes are in-
fluenced by prior exercise. Despite the integral role of splanch-
nic tissues in glucoregulation, very little is known about how
these tissues function after the added metabolic demands
placed upon them by physical exercise.
After exercise, liver and muscle glycogen stores are de-
pleted and gluconeogenic efficiency and lipolysis are elevated (6).
Furthermore, basal (1, 6, 7) and glucose-stimulated (2, 4, 5, 8)
insulin levels are often reduced. Adaptations after exercise
compensate for reduced circulating insulin at the muscle (9).
However, it is unclear whether hepatic sensitivity to insulin or
any other determinant of hepatic glucose metabolism is in-
creased in a similar manner. It was the aim of these studies to
determine whether the gut and liver adapt after exercise to fa-
cilitate the disposition of oral glucose. Specifically, the work
herein describes the influence of prior exercise and in-
traduodenal glucose on (
a
) intestinal glucose absorption; (
net hepatic glucose uptake and its determinants (e.g., hepatic
glucose load, insulin, arterial-portal vein glucose gradient); (
partitioning of glucose between oxidative and nonoxidative
processes within the liver and skeletal muscle; and (
tioning of carbons between splanchnic bed and previously
working limb. These aims were assessed using dual isotopic
methods in a chronically catheterized conscious dog model.



b

)

c

)

d

) parti-

Methods

Animal maintenance and surgical procedures.
mean wt 20.8
?
0.4 kg) of either gender that had been fed a standard
diet (beef dinner from Kal Kan, Vernon, CA and Wayne Lab Blox:
51% carbohydrate, 31% protein, 11% fat, and 7% fiber based on dry
weight, Allied Mills, Inc., Chicago, IL) were studied. The dogs were
housed in a facility that met American Association for the Accredita-
tion of Laboratory Animal Care guidelines and the protocols were
approved by the Vanderbilt University School of Medicine Animal
Care Committee. At least 16 d before each experiment a laparotomy
was performed under general anesthesia (sodium pentobarbital, 25
mg/kg). Silastic catheters (0.03 ID) were inserted into the vena cava

Mongrel dogs (

n



?

15;


Address correspondence to David H. Wasserman, Ph.D., Light Hall
Rm. 702, Department of Molecular Physiology and Biophysics,
Vanderbilt University School of Medicine, Nashville, TN 37232.
Phone: 615-343-7335; FAX: 615-322-7236; E-mail: david.wasser-
man@mcmail.vanderbilt.edu
Received for publication 10 January 1996 and accepted in revised
form 10 April 1996.

Page 2

126

Hamilton et al.

for tracer and indocyanine green infusions. A silastic catheter (0.08
ID) was inserted through the duodenal mucosa 3–4 cm below the py-
lorus for infusion of glucose (cold and U-[
with a purse string stitch. Silastic catheters (0.04 ID) were inserted
into the portal vein and left common hepatic vein for blood sampling.
Incisions were also made in the neck region and inguinal region for
the placement of arterial and common iliac vein sampling catheters,
respectively. The carotid artery was isolated and a silastic catheter
(0.04 ID) was inserted so that its tip rested in the aortic arch. A silas-
tic catheter (0.03 ID) was introduced into the common iliac vein via a
lateral circumflex vein. Exposure of the lateral circumflex vein was
achieved with a 2-cm incision in the lower femoral region and dissec-
tion of the vein from the subcutaneous tissues. The catheter tip was
positioned in the common iliac vein, distal to the anastomosis with
the vena cava. The median sacral vein was ligated to prevent dilution
from other sites. Verification of catheter placement was made
through the abdominal incision site. After insertion, the catheters
were filled with saline containing heparin (200 U/ml; Abbott Labora-
tories, North Chicago, IL) and their free ends were knotted.
Doppler flow probes (Instrumentation Development Laboratory,
Baylor University School of Medicine, Waco, TX) were used to mea-
sure portal vein, hepatic artery, and external iliac artery blood flows
(10). Briefly, a small section of the portal vein, upstream from its
junction with the gastroduodenal vein, was cleared of tissue, and a
7.0-mm ID flow cuff was placed around the vessel and secured. The
gastroduodenal vein was isolated and then ligated proximal to its coa-
lescence with the portal vein. A section of the main hepatic artery ly-
ing proximal to the portal vein was isolated and a 3.0-mm ID flow cuff
was placed around the vessel and secured. The external iliac artery
was accessed from the abdominal incision, dissected free of surround-
ing tissue, and fitted with a 6.0-mm ID flow probe cuff which was then
secured around the vessel. The Doppler probe leads and the knotted
free catheter ends, with the exception of the carotid artery and com-
mon iliac vein catheters, were stored in a subcutaneous pocket in the
abdominal region so that complete closure of the skin incision was
possible. The carotid artery and the common iliac vein catheters were
stored under the skin of the neck and inguinal regions, respectively.
Starting 1 wk after surgery, dogs were exercised on a motorized
treadmill, regardless of whether they were used for sedentary or exer-
cise experiments, so that they would be familiar with treadmill run-
ning. Animals were not exercised during the 48 h preceding an exper-
iment. Only animals that had (
a
) a leukocyte count
a hematocrit
?
36%, (
c
) normal stools, and (
suming all of the daily ration) were used.
Studies were conducted after an 18-h fast, since this allows for
complete meal absorption in the dog
ment, the subcutaneous ends of the catheters were freed through
small skin incisions made under local anesthesia (2% lidocaine; Astra
Pharmaceutical Products, Worcester, MA) in the abdominal and
neck regions. The contents of each catheter were aspirated and they
were flushed with saline. Silastic tubing was connected to the exposed
catheters and brought to the back of the dog where they were secured
with quick drying glue. Saline was infused in the arterial catheter
throughout experiments (0.1 ml/min).
Experimental procedures.
Animals were either exercised at a
moderate intensity (100 m/min, 12% grade) on a motorized treadmill
(
n

?
7) or remained sedentary (
n

riod (t
?

?
180 to
?
30 min). The exercise intensity and duration used
in these experiments has been shown previously to result in a twofold
increase in heart rate (12) and an increase in O
maximum (13). Furthermore, a fall in liver glycogen from 35
13
?
3 grams results (6). A period of exercise recovery or continued
rest followed (t
?

?
30 to 150 min). Glucose (50% dextrose), mixed
with U-[C]glucose to give a specific activity of
given as a primed infusion (150 mg/kg; 8 mg/kg
num from t
?
0 to 150 min. At t
?
(42
?
Ci) and sodium C-bicarbonate (0.64
stant rate venous infusions of 3-[

14

C]glucose) and secured



?

18,000/mm

3

, (

b

)





d

) a good appetite (con-



(11). On the day of the experi-









?

8) for a corresponding time pe-







2

uptake to 50% of

?

4 to







14


?
?
min) into the duode-
70 min primers of 3-[
?
Ci/kg) were given. Con-
H]glucose (0.30
?

8,700 dpm/mg, was








?


3

H]glucose



14




3



Ci/min) and in-
docyanine green (0.1 mg/m
These infusions were continued for the duration of the study. Iso-
topes were obtained from New England Nuclear (Boston, MA) and
indocyanine green was purchased from Hynson, Westcott, and Dun-
ning (Baltimore, MD). Arterial samples were drawn at 5-min inter-
vals from t
?

?
20 to 0 min and at 15-min intervals from 0 to 150 min.
Portal, hepatic, and common iliac vein samples were drawn at t
?
10, 0, 15, 30, 60, 90, 120, and 150 min. Portal or hepatic vein catheter
failure occurred in three experiments and consequently
sampling could not be performed. Portal vein, hepatic artery, and ex-
ternal iliac artery blood flows were recorded continuously from the
frequency shifts of the pulsed sound signal emitted from the Doppler
flow probes (10). At the cessation of the experiment animals were
anesthetized using sodium pentobarbital, an abdominal midline inci-
sion was made, and
?
2-gram biopsies were taken from each of the
seven lobes of the liver. An incision was then made on the medial as-
pect of the left hindlimb and
?
2-gram biopsies were taken from
three hindlimb skeletal muscles (gastrocnemius, gracilis, vastus later-
alis). Upon excising, all tissue samples were immediately freeze
clamped in liquid nitrogen. The time interval between the induction
of anesthesia and last biopsy was
?
Processing of blood and tissue samples.
and deproteinized blood were stored on dry ice until the completion
of the experiment. Samples were then stored at
analysis. Plasma glucose levels were determined by the glucose oxi-
dase method using a glucose analyzer (Beckman Instruments, Fuller-
ton, CA). For the determination of plasma glucose radioactivity (
and C), samples were deproteinized with barium hydroxide (Sigma
Immunochemicals, St. Louis, MO) and zinc sulfate (Sigma Immu-
nochemicals), placed over Dowex 50W-X8 (Bio Rad Laboratories,
Richmond, CA) and Amberlite (Rohm and Haas, Philadelphia, PA)
resins, the supernatant was evaporated, and reconstituted in 1 ml of
water and 10 ml of Ecolite (ICN Biomedicals, Irvine, CA). Radioac-
tivity was then determined by dual-label liquid scintillation counting
using a Beckman LS 5000TD. Whole blood lactate, glycerol, and glu-
cose concentrations were determined in samples deproteinized with
an equal volume of 8% perchloric acid by enzymatic methods (14) on
an AutoAnalyzer (Technicon, Tarrytown, NY) or on a Monarch 2000
centrifugal analyzer (Instrumentation Laboratories, Lexington, MA).
Enzymes used in analyses of metabolites and amino acids were ob-
tained from Sigma Immunochemicals or Boehringer-Mannheim Bio-
chemicals (Mannheim, Germany). Whole blood lactate and glucose
radioactivities were measured on the deproteinized whole blood su-
pernatant by an established method (15). The
was liberated by acidification with hydrochloric acid and trapped on
chromatography paper using hyamine hydroxide.
Liver and muscle glycogen mass and radioactivity were measured
by a previously described method (16). Glycogen synthase activity
was determined in the absence of glucose 6-phosphate and in the
presence of 10 mM glucose 6-phosphate by the method of Golden et
al. (17). Glucose phosphorylating activity in liver (glucokinase) and
skeletal muscle (hexokinase) homogenates was measured by a previ-
ously described method (18).
Immunoreactive insulin was measured using a double antibody
system (interassay coefficient of variation [CV]
noreactive glucagon (3,500 mol wt) was measured in plasma samples
containing 50
?
l of 500 KIU/ml Trasylol (FBA Pharmaceuticals, New
York) using a double antibody system (interassay CV of 7%) modi-
fied from the method developed by Morgan and Lazarow for insulin
(19). Glucagon and insulin antisera were obtained from Dr. R.L. Gin-
gerich (Washington University School of Medicine, St. Louis, MO),

2



?

min) were also initiated at this time.





?



?

20,



trans

-hepatic






5 min.


After centrifugation plasma

?

70

?

C until later

3

H

14


?


14

CO

2

in whole blood

1

of 10%) (19). Immu-


1.
hepatic artery blood flow; NEFA, nonesterified fatty acid; PVF, por-
tal vein blood flow;
R
a
, glucose appearance;
ance; SA, specific activity.

Abbreviations used in this paper:

CV, coefficient of variation; HAF,




R

d

, glucose disappear-

Page 3

Prior Exercise and Splanchnic Glucose Metabolism

127

and the standard glucagon and
Research Institute (Copenhagen, Denmark). Standard insulin and
125
I-insulin were obtained from Linco Research Inc. (St. Louis, MO).
Plasma norepinephrine and epinephrine levels were determined us-
ing an HPLC technique (interassay CV of 11 and 13%, respectively)
(20). Plasma cortisol was measured using the Clinical Assays Gamma
Coat™ Radioimmunoassay Kit (Clinical Assays, Travenol-Genetech
Diagnostics, Cambridge, MA) (interassay CV of 6%).
Calculations.
Total glucose appearance (
(
R
d
) were determined by non–steady state equations for isotope
(3-[H]glucose) dilution (21) using a pool fraction of 0.65 (22). He-
patic [ C]glucose production was determined in a manner analogous
to the measurement of
R
a
, with the difference being that the specific
activity (SA) was the ratio of [ H]glucose to [
the ratio of [H]glucose to glucose. The systemic rate of appearance
of the intraduodenal glucose load was calculated by dividing the he-
patic [C]glucose production by the intraduodenal infusate SA. En-
dogenous
R
a
was calculated as the total
appearance of the intraduodenal glucose load. The systemic appear-
ance of intraduodenal glucose will be overestimated by an amount that
is dependent on the rate that [C]glucose is recycled. As a consequence,
endogenous
R
a
will be underestimated by the same magnitude.
Net hepatic lactate, glucose, and
by the formula HAF
?
([H]
?
[A])
[P], and [H] are the arterial, portal vein, and hepatic vein substrate
concentrations and HAF and PVF are the hepatic artery and portal
vein blood flows. These calculations were performed using Doppler-
determined blood flow measurements except in one experiment in
which probe failure required the use of results obtained using the dye
extraction method. The dye extraction technique measures total he-
patic blood flow but does not differentiate between inputs from the
portal vein and hepatic artery. In the experiment that was reliant on
the dye extraction technique, portal vein blood flow was assumed to
be 80% of total hepatic blood flow (23). The load of glucose reaching
the liver equals [P]
?
PVF
?
[A]
?
culated as PVF
?
([P]
?
[A]) and net splanchnic glucose balances
were calculated as (HAF + PVF)
?
Net limb balances were calculated as LF
blood (or plasma) flow through the external iliac artery and [I] is the
substrate level in the common iliac vein. The sign was reversed for the
calculation of limb CO
2
production. Limb fractional glucose extrac-
tion was calculated as the net limb glucose uptake divided by the limb
glucose load, which was considered equal to LF ? [A]. Blood levels
and flows were used for the calculation of all hepatic and limb bal-
ances. The ratio of blood to plasma glucose was calculated for the
basal period and the glucose infusion period for each dog at each of

125

I-glucagon were obtained from Novo








R

a

) and disappearance




3


14





3


14

C]glucose instead of

3


14





R

a

minus the systemic rate of

14





14

CO
PVF

2

balances were determined
?
([H]
?
[P]), where [A],





?











HAF. Net gut balances were cal-






([H]

?

[A]).
?


([A]

?

[I]). LF is limb

14



the four sampling sites. Plasma glucose values were then multiplied
by their corresponding ratio (i.e., blood glucose/plasma glucose) to
convert to blood glucose concentrations. The advantage of using
plasma glucose measurements is that a large number of replicates can
be done quickly and at little added cost. The ability to measure repli-
cate samples reduces the measurement CV. The conversion to blood
values alleviates the need for assumptions regarding the equilibration
of substrates between red cell and plasma water.
Hepatic conversion of glucose to CO2 was calculated as the net
hepatic 14CO2 production rate divided by the hepatic [14C]glucose
precursor SA. The precursor SA was considered to be the [14C]glu-
cose SA in the inflowing blood to the liver and was calculated as
({portal vein [14C]glucose SA} ? PVF ? {artery [14C]glucose SA} ?
HAF)/(HAF ? PVF). Since, during a [14C]glucose infusion [14C]lac-
Figure 1. Arterial plasma insulin (top) and glucagon (bottom) dur-
ing an intraduodenal glucose load (8 mg/kg ? min) in sedentary
(open circles) and exercised (closed circles) dogs. Data are
mean?SE; n ? 8 and 7 sedentary and exercised dogs, respectively.
Plasma glucagon levels were significantly elevated after exercise
from ?20 to 30 min (P ? 0.05–0.001).
Table I. Arterial Plasma Concentrations of Cortisol, Norepinephrine, and Epinephrine in Sedentary and Exercised Dogs before
and during Intraduodenal Glucose
Pre-glucose load
Intraduodenal glucose
15 min30 min 60 min90 min120 min150 min
Arterial plasma cortisol (?g/dl)
Sedentary
Prior exercise
Arterial plasma norepinephrine (pg/ml)
Sedentary
Prior exercise
Arterial plasma epinephrine (pg/ml)
Sedentary
Prior exercise
2.0?0.4
3.7?0.6*
3.7?0.9
6.8?1.7
4.4?1.2
7.7?1.9
5.1?1.3
7.0?2.7
3.8?0.7
5.0?1.7
4.8?1.4
5.3?1.4
4.2?1.5
3.6?1.6
128?21
187?44
130?20
152?26
132?26
159?19
128?18
159?24
124?13
137?24
110?12
165?45
117?12
158?32
83?10
137?23*
96?30
133?38
128?34
115?32
110?24
102?21
92?21
80?26
87?15
93?24
94?28
124?37
Data are mean?SE. n ? 8 and 7 in sedentary and exercised animals, respectively. *Values are significantly different compared with sedentary ani-
mals (P ? 0.05–0.002).

Page 4

128
Hamilton et al.
tate accumulates, it is necessary to consider lactate SA in the calcula-
tion of precursor SA when [14C]lactate uptake is present. In these ex-
periments, lactate was predominantly produced by the liver and,
therefore, was not included in the calculation of hepatic glucose me-
tabolism. Net limb lactate uptake was present during the intraduode-
nal glucose infusion requiring that lactate SA be considered in the
precursor SA for limb glucose conversion to CO2. Limb glucose ?
lactate oxidation was calculated as the limb 14CO2 output divided by
the sum of the SAs of glucose and lactate weighted for their respec-
tive net limb uptakes. Limb nonoxidative glucose ? lactate metabo-
lism was determined as the difference between net limb glucose ? lac-
tate uptake and oxidation. Inclusion of lactate SA into these
calculations resulted in a ? 5% change when compared with values
obtained when lactate was not considered. Assumptions involved in
these calculations have been described in detail previously (24, 25).
Net glycogen deposition in liver and muscle during intraduodenal
glucose was calculated as the fraction of glycogen derived from blood
glucose (mean [14C]glucose precursor SA during the intraduodenal
infusion/[14C]glycogen SA) multiplied by the glycogen content of the
liver. Cold and radioactive liver glycogen concentrations were the
mean of biopsy measurements from all liver lobes.
Statistics were performed using SuperAnova (Abacus Concepts,
Inc., Berkeley, CA) on a Macintosh PowerPC. Statistical compari-
sons between groups and over time were made using ANOVA de-
signed to account for repeated measures. Specific time points were
examined for significance using contrasts solved by univariate re-
peated measures. Statistics are reported in the corresponding table or
figure legend for each variable. Differences were considered signifi-
cant when P values were ? 0.05. Data are expressed as mean?SE.
Results
Arterial plasma hormone levels. Intraduodenal glucose elic-
ited a fourfold increase in arterial plasma insulin levels which
was equivalent in sedentary and exercised dogs (Fig. 1). Gluca-
gon levels (Fig. 1) were significantly elevated after exercise
(62?6 pg/ml) compared with sedentary animals (39?2 pg/ml).
Glucagon levels remained elevated at t ? 15 and 30 min of in-
traduodenal glucose. Table I shows that the arterial plasma
cortisol, norepinephrine, and epinephrine levels were elevated
after exercise before the intraduodenal glucose infusion. Dif-
ferences in cortisol and epinephrine levels between exercised
and sedentary animals were significant (P ? 0.05). Although
there was a tendency for cortisol to be higher during the in-
traduodenal glucose load, no significant differences between
groups were present.
Arterial plasma glucose levels and whole body glucose
fluxes. Arterial plasma glucose was not significantly different
in sedentary and exercised dogs before the intraduodenal glu-
Figure 2. Arterial plasma glucose (top), total glucose appearance
(middle), and glucose disappearance (bottom) during an intraduode-
nal glucose load (8 mg/kg ? min) in sedentary (open circles) and exer-
cised (closed circles) dogs. Data are mean?SE; n ? 8 and 7 sedentary
and exercised dogs, respectively, for arterial plasma glucose and n ?
8 and 6 sedentary and exercised dogs, respectively, for total glucose
appearance and disappearance. Arterial plasma glucose was signifi-
cantly higher in exercised dogs at t ? 15, 30, 60, 75, 120, and 135 min
(P ? 0.02–0.001). Total glucose appearance was significantly higher
in exercised dogs at t ? 15 and 45 min (P ? 0.05–0.01).
Figure 3. Systemic appearance of glucose from the intestine (top) and
liver (bottom) during an intraduodenal glucose load (8 mg/kg ? min)
in sedentary (open circles) and exercised (closed circles) dogs. Data
are mean?SE; n ? 8 and 6 sedentary and exercised dogs, respec-
tively. Systemic appearance of intraduodenal glucose was signifi-
cantly higher after exercise throughout the intraduodenal glucose in-
fusion period (P ? 0.02–0.01). Endogenous glucose production was
suppressed to a greater extent during intraduodenal glucose in exer-
cised dogs at t ? 30, 45, 75, 90, and 105 min (P ? 0.05–0.005).

Page 5

Prior Exercise and Splanchnic Glucose Metabolism
129
cose infusion (Fig. 2). It rose to a greater extent with in-
traduodenal glucose in exercised dogs. The larger increase in
arterial glucose after exercise occurred due to a more rapid in-
crease in total Ra as compared with sedentary dogs in the first
15 min. Glucose clearance (Rd divided by arterial glucose
level) increased similarly in sedentary and exercised dogs over
that same period.
Splanchnic glucose metabolism. The exaggerated initial in-
crease in total glucose appearance after exercise was due to a
greater systemic appearance of intraduodenal glucose (Fig. 3).
The systemic appearance of intraduodenal glucose was ? 2
mg/kg ? min greater after exercise throughout the infusion pe-
riod. Splanchnic glucose output was elevated in exercised ani-
mals compared with the sedentary group before the in-
traduodenal infusion (2.4?0.4 vs. 0.9?0.3 mg/kg ? min) and
rose to a greater extent during infusion (4.5?0.7 vs. 2.1?0.9
mg/kg ? min at t ? 150 min) (Fig. 4).
The reason for the increases in the systemic appearance of
intraduodenal glucose and net splanchnic glucose output after
exercise relates to effects of exercise on gut and liver glucose bal-
ances. Net gut glucose output during intraduodenal glucose
was accelerated by prior exercise reaching a rate of 5.6?0.7 mg/kg
? min at t ? 150 min compared with a rate of 3.0?1.0 mg/kg ?
min in sedentary animals (Fig. 4). Net hepatic glucose output
was ? 70% greater in the control period after exercise com-
pared with rest (Fig. 4). Nevertheless, net hepatic glucose up-
take was not significantly different in response to intraduode-
nal glucose. Fig. 3 shows that endogenous Ra, while similar
before intraduodenal glucose in the two protocols, was reduced
to a lower rate (? 1 mg/kg ? min) during intraduodenal glucose
after exercise. The hepatic glucose load and the portal vein to
arterial glucose gradient, both stimulators of hepatic glucose
uptake, were unaffected and increased by prior exercise, re-
spectively (Table II). Although the tracer-determined systemic
appearance of intraduodenal glucose is determined by the gut
and hepatic glucose balances, the response of these variables
determined by arteriovenous differences is somewhat different
than the tracer-determined variable. The balances rapidly ob-
tain plateau rates during glucose loading, while the tracer-
determined systemic appearance of intraduodenal glucose
continues to rise gradually after an initial rapid rise. The gradual
rise phase may reflect the contribution of [14C]glucose recy-
cling.
Hepatic glucose oxidation (Fig. 5) was significantly greater
in response to intraduodenal glucose in sedentary compared
with exercised dogs reaching rates of 0.78?0.14 and 0.40?0.13
mg/kg ? min, respectively, during the last 60 min of intraduode-
nal glucose.
Limb glucose metabolism. Net limb glucose uptake (Fig. 6)
was elevated during the control period approximately twofold,
in the exercised dogs. During intraduodenal glucose infusion it
Figure 4. Net gut (top), hepatic (middle), and splanchnic (bottom)
glucose balances during an intraduodenal glucose load (8 mg/kg ?
min) in sedentary (open circles) and exercised (closed circles) dogs.
Data are mean?SE; n ? 6 dogs in each protocol. Net gut glucose out-
put during intraduodenal glucose was greater after exercise at t ? 15,
60, 120, and 150 min (P ? 0.05–0.005). Net hepatic glucose output was
greater in the basal period after exercise (P ? 0.02). Net splanchnic
glucose output was greater after exercise at t ? ?10, 30, 60, 90, 120,
and 150 min (P ? 0.02–0.01).
Table II. Arterial Plasma Concentration and Portal-Vein Plasma Glucose Gradient in Sedentary and Exercised Dogs before and
during Intraduodenal Glucose
Pre-glucose load
Intraduodenal glucose
15 min30 min60 min 90 min120 min 150 min
Hepatic glucose load (mg/kg·min)
Sedentary
Prior exercise
Arterial-portal vein blood glucose (mg/dl)
Sedentary
Prior exercise
23?2
20?1
34?4
35?5
38?4
36?5
38?2
39?4
39?4
36?3
37?3
36?3
33?3
33?4
3?1
3?1
?13?4
?34?6*
?16?3
?31?3*
?11?4
?30?7*
?15?4
?28?3*
?15?3
?29?3*
?13?5
?29?4*
Data are mean?SE. n ? 6 in both protocols. *Values are significantly different compared with sedentary animals (P ? 0.001).