Glucose Homeostasis
 brain has high consumption of glucose
– uses ~20% of RMR
– 1° fuel for energy
 during exercise, working muscle competes
with brain for glucose
 many redundant systems for maintaining
glucose homeostasis
– hepatic glucose production (glycogen, lactate,
pyruvate, glycerol, alanine)
– pancreatic hormones (insulin, glucagon)
– sympathoadrenal stimulation (epinephrine)
Claude Bernard
(1813-1878)
 Discovery of new
function of liver-glucose secretion
into blood (1848)
– Previously thought
that only plants could
produce sugar
– Sugar must be taken
in by diet
Glucose Production
During Exercise
Maintenance of Blood Glucose
 glucose needed for CNS, ATP synthesis,
Kreb’s cycle intermediates
  muscle glucose uptake (Rd) matched by 
liver glucose release (Ra)
– glucose pool = ~5 g (~20 kcal)
– dependent upon exercise intensity and duration
 endurance exercise may need CHO ingestion
to maintain blood [glucose]
Cori Cycle
Liver Gluconeogenesis
 uses pyruvate & lactate (Cori cycle),
glycerol, and alanine (glucosealanine cycle) as substrates
 liver contains glucose 6-phosphatase
and other enzymes that allow
reversal of glycolysis and release of
glucose
Gluconeogenic amino acids
 urea formation from excreted N in amino acid
degradation
 C skeletons are degraded into:
– glucose
– ketone acetoacetate or acetyl Co-A
 during fasting, starvation, and prolonged exercise,
AA supply most of C used in gluconeogenesis
– glucose-alanine cycle
 AA metabolism contributes 10-15% of total
substrates used during exercise
Glucosealanine cycle
leucine
Leucine is 1°
BCAA that
provides N for
alanine
formation. This
model may not
operate when
glucose &
glycogen is low
Interrelationship of
leucine catabolism and
alanine formation
Rate of appearance (Ra) of
alanine (a) and leucine N
transfer to alanine (b) at
rest and during exercise
Wolf et al., 1982, 1984
Regulation of liver glucose output
 glucose threshold stimulates liver glucose output
– hypoglycemia stimulates hormonal response (EPI,
glucagon, cortisol, GH)
– glucose threshold is dynamic
 like blood, glucose uptake is shunted to active
tissue
– skeletal muscle GLUT transporters
• GLUT1 is 1º transporter at rest
• GLUT4 is 1º transporter during exercise
Endocrine Regulation of Glucose
Homeostasis
 Insulin—secreted from pancreatic islet ß cells
– released regulated by blood [glucose] (glycemic threshold)
– stimulates glucose oxidation & storage and inhibits glucose
production
•
•
•
•
stimulates glycogen synthase
inhibits phosphorylase
inhibits gluconeogenesis
stimulates glucose transport into adipocytes, which is then
converted into TG
• inhibits hormone-sensitive lipase (HPL) ( cAMP) and
lipoprotein lipase
• activates GLUT1
– release inhibited by EPI and NE
– obesity increases and training decreases insulin secretion
Endocrine Regulation of Glucose
Homeostasis
 Glucagon—secreted from pancreatic islet 
cells
– promotes liver mobilization of fuels
– stimulates cAMP
– released regulated by blood [glucose] (glycemic
threshold)
– Activates phosphorylase
– Stimulates gluconeogenesis
Endocrine Regulation of Glucose
Homeostasis
 Epinephrine—secreted from adrenal
medulla
– released in response to exercise and
decreased blood [glucose]
• stimulates liver and muscle phosphorylase a
and PFK
• increases liver glucose output and muscle
glucose metabolism
Glucose Homeostasis
During Exercise
Effect of CHO feeding during
exercise on glucose homeostasis
Hepatic glucose output
(HGP) and glucose uptake
(Rd) w/ and w/out CHO
feedings during prolonged
exercise (~70% of VO2max)
McConell et al., JAP, 1994
CHO Feeding during Prolonged
Exercise






 blood glucose
maintains CHO oxidation rate
 time to exhaustion/performance
conserves liver glycogen
 muscle glucose uptake
no effect on muscle glycogen utilization
Effects of Prolonged Exercise on
Blood Glucose
Glucose Uptake (mmol/min)
Muscle Glucose Uptake
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0
30
60
90
Time (min)
120
150
180
Blood Glucose
6.0
Glucose (mM)
5.0
4.0
3.0
2.0
1.0
0.0
0
30
60
90
Time (min)
120
150
180
Liver Glycogen
60
Glycogen (g/kg)
50
40
30
20
10
0
0
30
60
90
Time (min)
120
150
180
Glucose Output (mmol/min)
Liver Glucose Output
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
0
30
60
90
Time (min)
120
150
180
Blood Glucagon
Glucagon (pg/ml)
300
250
200
150
100
50
0
30
60
90
Time (min)
120
150
180
Blood Insulin
1.2
Insulin (uU/ml)
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0
30
60
90
Time (min)
120
150
180
Blood Epinephrine
1.6
Epinephrine (ng/ml)
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0
30
60
90
Time (min)
120
150
180
Effect of exercise intensity on liver
glucose output
Liver glucose output from
gluconeogenesis (GNG) and
glycogenolysis (GLY) during
prolonged exercise at 30% of
VO2max
Effects of Incremental Exercise
on Blood Glucose
Blood Glucose
7
Glucose (mM)
6
5
4
3
2
1
0
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Treadmill Speed (mph)
Blood Epinephrine
Epinephrine (ng/ml)
0.6
0.5
0.4
0.3
0.2
0.1
0
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Treadmill Speed (mph)
Blood Insulin
1.2
Insulin (uU/ml)
1.0
0.8
0.6
0.4
0.2
0.0
2
3
4
5
6
7
8
9
10 11 12 13 14 15
Treadmill Speed (mph)
Effect of exercise intensity on liver
glucose output
Liver glucose output from
gluconeogenesis (GNG) and
glycogenolysis (GLY) during
prolonged exercise at 30% of
VO2max
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 Scientific process
– research question & hypothesis
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