Effects of Intense and Prolonged Exercise
on Insulin Sensitivity and Glycogen Metabolism
in Hypertensive Subjects
Caroline Rhéaume, MSc; Paulo-Henrique Waib, MD, PhD; N’Guessan Kouamé, PhD;
André Nadeau, MD; Yves Lacourcière, MD; Denis R. Joanisse, PhD;
Jean-Aimé Simoneau, PhD†; Jean Cléroux, PhD
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Background—The information that insulin sensitivity and glycogen synthesis are reduced in hypertension arises primarily
from studies using insulin infusions. Whether glycogen metabolism is actually altered in a physiological condition, such
as during and after prolonged exercise, is currently unknown.
Methods and Results—To examine this issue, 9 hypertensive and 11 normotensive subjects were evaluated on a rest day
and after intense and prolonged exercise on a separate day. Insulin sensitivity and hemodynamic variables were
measured on both days. On the exercise day, whole-body substrate utilization was assessed and muscle biopsies were
taken in the leg at baseline, immediately after exercise, and 2.5 and 4 hours after exercise. Insulin sensitivity at rest was
lower in hypertensive than normotensive subjects (P⬍0.05) and increased after exercise in normotensive (P⬍0.01) but
not in hypertensive (P⫽NS) subjects. Leg blood flow increased after exercise in both groups but to a lesser extent in
hypertensive than normotensive subjects. Baseline glycogen content and maximal glycogen synthase activity were
higher in hypertensive than normotensive subjects (P⬍0.001). Glycogen concentration decreased relatively less (⫺35
versus ⫺66%) and returned to baseline levels faster in hypertensive subjects after exercise. Hypertensive subjects used
⬇40% less carbohydrates during exercise (P⬍0.001) at the expense of greater free fatty acid oxidation.
Conclusions—It is concluded that increased intramuscular glycogen storage and resynthesis in hypertension are
independent of blood flow and may represent compensatory mechanisms for the reduced insulin sensitivity and
carbohydrate metabolism in this condition. (Circulation. 2003;108:2653-2659.)
Key Words: exercise 䡲 insulin 䡲 glycogen 䡲 hypertension
S
everal epidemiological studies have indicated that hypertension is an insulin-resistant state independent of obesity.1,2 It has been shown that whole-body insulin-induced
glucose uptake is reduced in hypertensive populations.3,4 The
impairment of insulin-mediated glucose utilization in hypertension appears to be restricted principally to nonoxidative
glucose disposal, ie, mainly glycogen synthesis in skeletal
muscles.3,5– 8 Defects in this pathway can alter the metabolism
of glucose and contribute to insulin resistance in muscle
tissue.9 Studies using intra-arterial infusions of insulin in the
forearm have found smaller arteriovenous glucose differences
in hypertensive than in normotensive subjects,10 suggesting
that glycogen synthesis in skeletal muscles is lower in
hypertensive patients, but the physiological relevance of these
findings has not been clearly established.
It was proposed that the pervasive relationship between
blood pressure elevation and decreased glucose extraction by
skeletal muscle may be secondary to hemodynamic factors.11,12 Insulin-induced glucose uptake during a hyperinsulinemic euglycemic clamp was positively correlated to capillary density and to percent slow-twitch fiber content of
different muscles.13 Slow-twitch fibers have a higher oxidative capacity, insulin binding, insulin sensitivity, basal glucose uptake, and a rich capillary supply than fast-twitch
fibers.14,15 Because a reduced proportion of slow-twitch fibers
was reported in hypertensive individuals,16 this alteration
could contribute to the increased insulin resistance in hypertension.17,18 These observations are consistent with the concept that insulin sensitivity could be related to skeletal muscle
blood flow and relative muscle fiber type.
We recently reported that changes in hemodynamics did
not contribute to the increased insulin sensitivity found after
30 minutes of mild exercise in hypertensive subjects.19 In the
present study, we used a more prolonged and intense exercise
Received October 17, 2002; de novo received April 4, 2003; revision received August 14, 2003; accepted August 17, 2003.
From the Hypertension (C.R., P.-H.W., N.K., Y.L., J.C.) and Diabetes (A.N.) Research Units, Laval University Hospital Research Center, and the
Kinesiology Division, Laval University (D.R.J., J.-A.S.), Québec, Canada.
†Deceased.
Correspondence to Jean Cléroux, PhD, HDQ Research Center, 9, rue McMahon, Québec, Québec, Canada G1R 2J6. E-mail
[email protected]
© 2003 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/01.CIR.0000097112.25429.FB
2653
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November 25, 2003
protocol of Boulay et al.20 During exercise, blood samples were
taken to measure insulinemia and glycemia. Three hours after the
end of exercise, all subjects received a second intravenous glucose
bolus (identical to that given during the measurement of insulin
sensitivity) to help replenish muscle glycogen stores. These techniques are explained briefly below, because most have been described in detail elsewhere.19,21
Measurements
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Figure 1. Illustration of study protocol. Insulin sensitivity and
hemodynamic variables were measured (1) on a control rest day
and (2) on an exercise day in random order. On exercise day, all
subjects exercised on a cycle ergometer at ⬇70% of V̇Omax during 90 minutes. Muscle biopsies were made before exercise,
immediately after exercise, and 2.5 and 4 hours after exercise.
An intravenous glucose bolus was given on control rest day, 0.5
hour after end of exercise, and 3 hours after end of exercise.
protocol to reduce intramuscular glycogen content. We also
examined exercise substrate metabolism and postexercise
hemodynamics, insulin sensitivity, and glycogen resynthesis
in hypertensive and normotensive subjects. The primary goals
of the present study were therefore to determine whether the
insulin-resistant state of hypertension was associated with
altered intramuscular glycogen stores and/or substrate utilization during exercise as well as slower rates of glycogen
resynthesis after prolonged exercise. Secondary goals were to
determine the role of skeletal muscle fiber type distribution,
blood flow, and glycogen synthase activity in any alteration
in glycogen synthesis in hypertension.
Methods
Patients with mild to moderate essential hypertension and agematched normotensive subjects gave their written informed consent
to participate in this study. The procedures followed were in
accordance with our institutional guidelines and the protocol approved by Laval University Hospital Research Center’s Ethics
Committee on Human Research. All hypertensive subjects underwent a 4-week screening period during which they visited the
Hypertension Clinic at our institution weekly, and antihypertensive
medication was stopped 1 month before the study in previously
treated patients. Peak oxygen uptake was measured 1 week before
the laboratory evaluations.
The subjects underwent 2 evaluations on separate days at 1-week
intervals in random order (Figure 1). On the control rest day and on
the exercise day, insulin sensitivity and hemodynamic variables were
measured in subjects fasting from midnight on. Hemodynamic
variables measured were blood pressure, heart rate, forearm blood
flow, and leg blood flow. On the exercise day, whole-body carbohydrate and lipid metabolisms were assessed during exercise, and
muscle biopsies were taken together with hemodynamic measurements at baseline, immediately after exercise, and 2.5 and 4 hours
after exercise (Figure 1). All subjects exercised on a cycle ergometer
at ⬇70% of peak oxygen uptake during 90 minutes according to the
Oxygen uptake and carbon dioxide production were determined by
analysis of expired gases. These values were used to calculate the
respiratory exchange ratio to assess amounts of carbohydrates and
fatty acids consumed during exercise.22 Peak oxygen uptake was
measured during an increased work test schedule on a cycle
ergometer with 50-W increments every 2 minutes until volitional
exhaustion. Blood pressure (mercury sphygmomanometer), heart
rate (from ECG), and forearm and leg blood flow (plethysmography)
were measured in sequence.
Insulin sensitivity was assessed with the method of Galvin et al23
from the ratio of glucose disappearance rate (Kg) over insulin area
under the curve (IAUC) during an intravenous glucose tolerance test as
previously described.19 The intravenous glucose tolerance test consisted of the injection of 20 g/m2 body surface area of 50% dextrose
in an antecubital vein within 3 minutes (Figure 1). Glucosuria was
measured over a period of 2 hours after the glucose bolus to assess
whether significant amounts were eliminated via this route and
whether differences were present between normotensive and hypertensive subjects.
Needle muscle biopsies were performed 4 times in the vastus
lateralis under local anesthesia (1% lidocaine hydrochloride) on the
exercise day (Figure 1) according to the method of Bergstrom.24
Percentage and area of type I, IIA, and IIB fibers were established by
the myofibrillar ATPase staining technique. Glycogen concentration
in specific fiber types was determined by staining transverse sections
with periodic acid–Schiff reagent. Glycogen-stained sections were
matched with serial sections stained for myosin ATPase for determination of exercise-induced depletion patterns in specific fiber
types. Glycogen concentrations are expressed in relative units (RU)
of staining intensity. Glycogen content was also measured by
calculating an index that takes into account the amount of glycogen
(RU) in each fiber type, the surface area (␮m2) of each fiber type, and
the proportion (percentage) of each fiber type with the following
equation: [(glycogen type I⫻surface type I⫻% fiber type I)⫹
(glycogen type IIA⫻surface type IIA⫻% fiber type IIA)⫹(glycogen
type IIB⫻surface type IIB⫻% fiber type IIB)]⫻10⫺6.
Glycogen synthase activity was measured as described by SchalinJantti et al,25 a modification of the method of Hornbrook et al.26
Glycogen synthase activity is expressed in micromoles of NAD
formed per minute per gram wet weight of muscle tissue. Glycogen
synthase activity was measured at 0.1 mmol/L of G6P substrate and
at 10 mmol/L of G6P substrate. The ratio of activity determined at
0.1 mmol/L of G6P to maximal activity determined at 10 mmol/L of
G6P (the fractional activity) reflects dephosphorylation and activation of glycogen synthase.
Statistical Analysis
Data are expressed as mean⫾SEM. Results were analyzed by
ANOVA for repeated measurements27 considering the interaction
between time (of measurement of a given variable) and group
(hypertensive and normotensive). When a significant (P⬍0.05) F
ratio was found, Fisher’s test was used to locate significant
differences.
Results
Nine male hypertensive subjects with mild to moderate
hypertension and 11 normotensive subjects participated in
this study. Hypertensive subjects were similar to normotensives in terms of age (44⫾3 and 40⫾2 years, respectively),
body weight (85⫾2 and 82⫾5 kg), height (176⫾2 and
Rhéaume et al
Exercise, Insulin, and Glycogen in Hypertension
2655
TABLE 1. Hemodynamic Variables Before Exercise (Baseline), Immediately After Exercise, and 2.5 and 4 Hours After Exercise in
Normotensive and Hypertensive Subjects During the Exercise Day
Baseline
Time/Variables
Immediately After
2.5 Hours After Exercise
NT
HT
NT
HT
SBP
117⫾3
142⫾4†††
109⫾4*
130⫾3**†††
NT
DBP
75⫾2
93⫾3†††
68⫾4*
85⫾3*†††
68⫾2**
89⫾4*†††
HR
62⫾2
62⫾2
79⫾3***
78⫾2***
70⫾3**
68⫾3**
FBF
4.0⫾0.7
4.0⫾0.3
3.5⫾0.5
3.2⫾0.2*
3.6⫾0.5
3.1⫾0.5*
LBF
2.5⫾0.3
2.8⫾0.1
3.0⫾0.2*
2.7⫾0.2
3.2⫾0.3**
FVR
26.9⫾3.1
28.0⫾1.9
25.6⫾2.3
33.5⫾3.2†
LVR
39.6⫾4.0
39.8⫾0.3
28.4⫾2.0*
38.1⫾2.5††
Time
HT
P
P
0.001
0.030
71⫾2*
89⫾4†††
0.001
0.043
70⫾3**
74⫾3**
0.87
0.001
3.5⫾0.5
3.1⫾0.3**
0.365
0.038
3.4⫾0.3*
2.8⫾0.3
3.2⫾0.3
0.435
0.047
28.0⫾4.0
39.8⫾5.0*
28.9⫾3.8
39.5⫾6.0*
0.005
0.023
29.0⫾2.7**
34.0⫾3.9
33.0⫾2.8*
37.0⫾4.4
0.037
0.028
143⫾4†††
NT
Group
142⫾4†††
116⫾4
HT
4 Hours After Exercise
116⫾3
NT and HT indicate normotensive and hypertensive subjects; SBP and DBP, systolic and diastolic blood pressure (mm Hg); HR, heart rate (bpm); FBF, forearm blood
flow (mL䡠dL⫺1䡠min⫺1); LBF, leg blood flow (mL䡠dL⫺1䡠min⫺1); FVR, forearm vascular resistance (units); and LVR, leg vascular resistance (units). Values are mean⫾SEM
of 11 normotensive and 9 hypertensive subjects. ANOVA probability levels for group effect (HT, NT) and time effect (baseline, immediately after exercise, 2.5 hours,
and 4 hours after exercise) are indicated at right.
*, **, and *** indicate significant differences at P⬍0.05, P⬍0.01, and P⬍0.001 from respective control value.
†, ††, and ††† indicate significant differences at P⬍0.05, P⬍0.01, and P⬍0.001 from respective value in normotensive subjects.
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178⫾2 cm), body surface area (2.0⫾0.1 and 2.0⫾0.1 m2),
and peak oxygen uptake (45⫾3 and 43⫾2 mL/kg per
minute). Clinic supine blood pressure of hypertensive subjects was higher than that of normotensive subjects (142⫾4/
93⫾3 and 117⫾3/75⫾2 mm Hg, respectively, P⬍0.001).
Four hypertensive subjects (44%) and 6 normotensive subjects (55%) had a normal glucose tolerance on the basis of a
glucose disappearance rate (Kg) ⬎1.5 min⫺1, 3 hypertensive
subjects (33%) and 5 normotensive subjects (45%) had an
intermediate glucose tolerance (1.0⬍Kg⬍1.5 min⫺1), and 2
hypertensive subjects (22%) had glucose intolerance (Kg⬍1.0
min⫺1).
During the 90-minute exercise period, hypertensive and
normotensive subjects exercised at similar workloads (135⫾5
and 152⫾9 W, respectively, P⫽NS), oxygen uptake (25⫾12
and 25⫾12 mL/kg per minute), and percent peak oxygen
uptake (68⫾2 and 73⫾2%, P⫽NS). Hypertensive subjects
had a significantly lower respiratory exchange ratio than
normotensives (0.80⫾0.01 versus 0.87⫾0.01, respectively,
P⬍0.001), indicating that they used ⬇40% less carbohydrates over the 90-minute exercise period (102⫾10 versus
174⫾11 g, P⬍0.001) at the expense of greater free fatty acid
oxidation (76⫾5 versus 49⫾4 g, P⬍0.001). Thus, 40% and
67% of the energy cost of exercise (⬇1250 kcal) was derived
from carbohydrate metabolism in hypertensive and normotensive subjects, respectively, and 60% and 33% from free
fatty acid oxidation.
Hemodynamic Results
Hemodynamic variables measured on the exercise day appear
in Table 1 (baseline hemodynamic variables measured on the
control rest day were similar, P⫽NS, data not shown). Blood
pressure was higher in hypertensive than normotensive subjects (P⬍0.001). Systolic and diastolic blood pressures were
significantly lower immediately after exercise than at baseline in both groups. Diastolic blood pressure was reduced 2.5
and 4 hours after exercise in normotensive but only at 2.5
hours in hypertensive subjects. Heart rate was similar in both
groups, and the small tachycardia after exercise was similar in
both groups (P⫽NS). Forearm and leg blood flows were
respectively similar in both groups (P⫽NS). Forearm blood
flow decreased significantly immediately after exercise and
2.5 and 4 hours after exercise in hypertensives, whereas it
remained unchanged in normotensives compared with baseline (P⬍0.05). Leg blood flow increased only 2.5 hours after
exercise (P⬍0.05) in hypertensives but had already done so
immediately after exercise in normotensives. Reciprocal
changes in vascular resistance relative to those in blood flow
were found in both groups.
Metabolic Results
Insulin Sensitivity
Baseline plasma glucose was not different in hypertensive
and normotensive subjects on the control rest day (5.4⫾0.2
and 5.2⫾0.2 mmol/L, respectively, P⫽NS) and on the
exercise day (5.2⫾0.2 and 5.0⫾0.1 mmol/L, respectively,
P⫽NS), whereas baseline plasma insulin was higher in
hypertensives than normotensives on the control rest day
(60⫾5 and 50⫾4 pmol/L, respectively, P⬍0.05) and the
exercise day (70⫾10 and 31⫾5 pmol/L, respectively,
P⬍0.01). At the end of 90 minutes of intense exercise,
glycemia was unchanged in hypertensive subjects
(5.4⫾0.3 mmol/L, P⫽NS) but was significantly reduced in
normotensives (4.6⫾0.2 mmol/L, P⬍0.5). Insulinemia was
reduced at the end of exercise in both groups, but to a lesser
extent in hypertensive than normotensive subjects (42⫾8 and
16⫾2 pmol/L, respectively, both P⬍0.01). At the beginning
of insulin sensitivity assessment (before the glucose bolus),
glucose and insulin levels were not different (P⫽NS) from
baseline values in each group (data not shown).
Insulin sensitivity (Kg/IAUC) was significantly lower in
hypertensive than normotensive subjects on the control rest
day (Figure 2). Insulin sensitivity increased after exercise in
normotensive subjects but not in hypertensive subjects (Figure 2). Glucose disappearance rate (Kg) was similar in
hypertensive and normotensive subjects on the control rest
day (1.6⫾0.3 and 1.7⫾0.1 min⫺1, respectively, P⫽NS) but
was significantly lower in hypertensive than normotensive
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Circulation
November 25, 2003
Figure 2. Line graphs illustrate individual insulin sensitivities
measured on control rest day and after exercise in normotensive
(NT) and hypertensive (HT) subjects. Circles lying outside individual data points represent mean⫾SEM. ** indicates significant
differences at P⬍0.01 from respective control value; † and ††
indicate significant differences at P⬍0.05 and P⬍0.01 from
respective value in normotensive subjects.
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subjects after exercise (1.3⫾0.3 and 1.9⫾0.3 min⫺1, respectively, P⬍0.05). Plasma insulin levels and IAUCs were similar
in both groups during the intravenous glucose tolerance test
on the control rest (IAUC values: HT, 14 578⫾2604 versus NT,
10 561⫾1348 pmol/L⫻min, P⫽NS) but were significantly
higher in hypertensives than in normotensives after exercise
(IAUC values: HT, 13 007⫾2091 and NT, 8405⫾965 pmol/
L⫻min, P⬍0.05).
Glucosuria measured over a period of 2 hours after the
glucose bolus was not different in hypertensive and normotensive subjects (control rest day values: 2.3⫾0.5 and
2.1⫾0.2 g, respectively, P⫽NS) and was not affected by the
previous exercise (P⫽NS).
Muscle Characteristics and Glycogen Content
The proportion, the surface area of different fiber types, and
the number of capillaries around the different muscle fibers
were similar in both groups of subjects (Table 2). Fasting
muscle glycogen concentration in each fiber type (Figure 3)
and the index of whole muscle glycogen content (Table 3)
were higher in hypertensive than normotensive subjects
(P⬍0.001). Glycogen content decreased immediately after
exercise in both groups (P⬍0.05). Muscle glycogen tended to
decrease less in hypertensives (⫺34⫾8 versus ⫺46⫾7 RU,
P⫽0.13), and this represented a significantly smaller proportion of muscle glycogen reserves in hypertensive than normotensive subjects (⫺35⫾8 versus ⫺66⫾8%, P⬍0.01).
Whereas glycogen remained below baseline up to 4 hours
after exercise in normotensive subjects, it increased back to
levels not different from baseline in hypertensive subjects 4
hours after exercise (Table 3 and Figure 3).
TABLE 2.
Figure 3. Glycogen content (RU) of type I fibers (A), type IIa
fibers (B), and IIb fibers (C) at baseline (Base), immediately after
exercise (0), and 2.5 and 4 hours after exercise. ††† indicates
significant differences (ANOVA) at P⬍0.001 between hypertensive and normotensive subjects.
Glycogen Synthase
Glycogen synthase measured at 0.1 mmol/L of G6P was not
different between groups (P⫽0.89) and increased to a similar
extent after exercise in both groups (P⬍0.001) (Figure 4).
Total glycogen synthase measured at 10 mmol/L of G6P
substrate was higher in hypertensive than normotensive
Muscle Characteristics of Hypertensive and Normotensive Subjects
Type I
Fibers Type/Variables
NT
Type IIA
HT
NT
Type IIB
HT
NT
HT
Proportion, %
44⫾3
43⫾4
40⫾4
39⫾2
17⫾2
18⫾3
Surface area, ␮m2⫻103
5.6⫾0.4
6.8⫾0.4
6.7⫾0.6
7.3⫾0.4
6.2⫾0.5
6.3⫾0.3
Capillaries, n
5.1⫾0.3
5.9⫾0.5
5.0⫾0.3
5.7⫾0.5
4.2⫾0.3
4.8⫾0.4
Values are mean⫾SEM of 11 male normotensive (NT) and 9 male hypertensive (HT) subjects. All
variables were similar in hypertensive and normotensive subjects (P⫽NS).
Rhéaume et al
Exercise, Insulin, and Glycogen in Hypertension
2657
TABLE 3. Skeletal Muscle Glycogen Content Index Integrating
Amount of Glycogen, Surface Area, and Proportion of Each
Fiber Type at Baseline and After Exercise in Normotensive and
Hypertensive Subjects
Glycogen Content Index
Variable/Time
Baseline
NT
73⫾8
HT
98⫾8†
After exercise
0h
28⫾9**
66⫾11*†
2.5 h
32⫾5**
61⫾10*†
4h
34⫾5**
76⫾10††
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Values are mean⫾SEM of 11 male normotensive (NT) and 9 male
hypertensive (HT) subjects. ANOVA probability levels for group effect (HT, NT)
and time effect (baseline, immediately after exercise 关0 h兴, and 2.5 and 4.0
hours after exercise) are indicated at right.
* and ** indicate significant differences at P⬍0.05 and P⬍0.001 from
respective control value.
† and †† indicate significant differences at P⬍0.05 and P⬍0.001 from
respective value in normotensive subjects.
subjects and was not affected by exercise (P⫽NS). As a
consequence, the fractional activity of glycogen synthase
increased after exercise in both groups (P⬍0.001) but to a
lesser extent (P⬍0.001) in hypertensive subjects (Figure 4).
Relationships Between Hemodynamic and
Metabolic Results
Insulin sensitivity did not correlate with percent composition
of muscle fiber type I in both groups (r⫽0.23, P⫽0.33).
Glycogen content index did not correlate with leg blood flow
in any situation (data not shown). A significant and inverse
correlation coefficient was found between insulin sensitivity
and maximal glycogen synthase activity after exercise
(r⫽0.47, P⬍0.05) but not before exercise (r⫽0.05, P⫽NS).
Discussion
The results of our study clearly show, first, that whole-body
carbohydrate utilization is reduced, that skeletal muscle
glycogen depletion is blunted, and that its repletion is more
pronounced after prolonged exercise in hypertension. Baseline and postexercise glycogen contents were higher in
hypertensive subjects. Second, total glycogen synthase activity is higher in hypertensive than normotensive subjects.
Third, similar muscle capillaries and muscle fiber type
distributions were found in both groups. These observations
will be discussed in the following paragraphs.
The present results confirm that hypertensive subjects are
insulin-resistant compared with normotensive subjects.10,19,28
Studies using insulin infusions have indicated that skeletal
muscle was presumably the main site of insulin resistance in
hypertension and that nonoxidative glucose disposal (ie,
mainly glycogen synthesis) was impaired.3,5– 8 Our hypertensive subjects had elevated baseline and postexercise glycogen
concentrations and rates of resynthesis in skeletal muscles
after prolonged exercise. The increased capacity for glycogen
resynthesis, ie, higher maximal glycogen synthase activity,
may be related to direct factors and/or represent compensa-
Figure 4. Glycogen synthase activity measured at 0.1 mmol/L of
G6P substrate (A), at 10 mmol/L of G6P substrate (B), and fractional activity (percent ratio of 2 activities, C) in muscle biopsy
samples taken at baseline (Base), immediately after exercise (0),
and 2.5 and 4 hours after exercise. ††† indicates significant differences (ANOVA) at P⬍0.001 between hypertensive and normotensive subjects.
tory adaptations to insulin resistance. Direct factors include
higher plasma glucose and insulin levels in the postexercise
period. This is supported by the fact that glycogen resynthesis
occurred importantly in type I fibers, ie, those particularly
sensitive to insulin. Alternatively, (1) the reduced insulininduced glucose transport (suggested by the inverse correlation between glycogen synthase and insulin sensitivity after
exercise) and/or (2) the reduced carbohydrate metabolism
during exercise and/or (3) the reduced ability to mobilize the
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November 25, 2003
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active fraction of glycogen synthase may promote a compensatory increase in glycogen resynthesis capacity.
A recent study by Solini et al9 reported normal levels of
glycogen and glycogen synthase activity in cultured skin
fibroblasts of hypertensive subjects with microalbuminuria
and reduced levels in diabetic subjects with and without
hypertension. Taken together, these results could indicate an
early compensatory adaptation in essential hypertension, ie,
increased intramuscular glycogen synthesis and glycogen
content (present study) that disappears in conditions with
progressively greater insulin resistance, such as hypertension
with microalbuminuria and diabetes (study by Solini et al9).
The results of our study do not support the hemodynamic
hypothesis of insulin resistance in hypertension,11,12 because
both groups examined were found to have similar muscle
capillaries, muscle fiber type distributions, and resting muscle
blood flows, whereas insulin resistance was reduced in
hypertensive subjects compared with normotensives. It is
possible that alterations of capillaries were undetected with
the histochemical method used in the present study. Hernandez et al29 did not find changes in capillaries with similar
histochemical methods but found abnormal capillary endothelial cells with electron microscopy. However, vasodilatation was reduced in hypertensive subjects during the hours
after prolonged exercise, whereas glycogen resynthesis occurred faster than in normotensive subjects. Furthermore,
glycogen content did not correlate with leg blood flow in
either group on any occasion.
Our present and previous results underline contrasting
adaptations in normotensive and hypertensive subjects after
exercise, depending on exercise intensity. Normotensive subjects did not demonstrate an increase in insulin sensitivity
after mild-intensity exercise19 but did so after higher-intensity
exercise (present study). These finding agree with other
reports in the literature as discussed previously.19 In hypertensive subjects, we found an increase in insulin sensitivity
after mild-intensity exercise in our previous study,19 whereas
no such change was found after intense and prolonged
exercise. The absence of an effect on insulin sensitivity in
hypertensive patients could be secondary to the lesser glycogen depletion and/or the higher free fatty mobilization and/or
the carryover of the higher adrenergic response after intense
and prolonged exercise. The mechanisms underlying these
contrasting adaptations in hypertension merit further
investigation.
In summary, whole-body carbohydrate and skeletal muscle
glycogen metabolisms are reduced during intense exercise in
hypertension, and postexercise glycogen resynthesis is enhanced. Elevated intramuscular glycogen content and resynthesis in hypertension do not appear to be related to either
chronic or postexercise vasodilatory changes. It is concluded
that increased intramuscular glycogen storage and resynthesis
in hypertension are independent of blood flow and may be
related to higher plasma glucose and insulin levels in the
postexercise period and/or represent compensatory mechanisms for the reduced insulin sensitivity and carbohydrate
metabolism in this condition.
Acknowledgments
This work was supported by grants to Dr Cléroux from the Heart and
Stroke Foundation of Canada, la Fondation des maladies du coeur du
Québec, and the Natural Sciences and Engineering Research Council
of Canada. Dr P.H. Waib was a recipient of a fellowship from the
Fundacao de Amparo à Pesquisa do Estado de Sao Paulo, Brazil. C.
Rhéaume was supported by studentships from the Heart and Stroke
Foundation of Canada, the Medical Research Council of Canada, le
Fonds de la recherche en santé du Québec, and the Fonds pour la
formation de chercheurs et l’aide à la recherche. We thank Rachelle
Duchesne and Marie Tremblay for expert assistance in performing
plasma glucose and insulin determinations and Mireille Marceau,
Yves Gélinas, and Jean-François Néron for expert technical assistance in various aspects of this study. Dr Germain Thériault’s
collaboration in performing initial biopsies is gratefully
acknowledged.
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Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Effects of Intense and Prolonged Exercise on Insulin Sensitivity and Glycogen Metabolism
in Hypertensive Subjects
Caroline Rhéaume, Paulo-Henrique Waib, N'Guessan Kouamé, André Nadeau, Yves
Lacourcière, Denis R. Joanisse, Jean-Aimé Simoneau and Jean Cléroux
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Circulation. 2003;108:2653-2659; originally published online October 27, 2003;
doi: 10.1161/01.CIR.0000097112.25429.FB
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