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
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]
Liver Gluconeogenesis
uses pyruvate & lactate (Cori cycle), glycerol, and alanine (glucose-alanine 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
Glucose-alanine cycle
Leucine is 1° BCAA that provides N for alanine formation. This model may not operate when glucose & glycogen is low
leucine
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
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
Muscle Glucose Uptake
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Liver glucose output from gluconeogenesis (GNG) and glycogenolysis (GLY) during prolonged exercise at 30% of VO2max
Effect of exercise intensity on liver glucose output
Blood Glucose
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Liver glucose output from gluconeogenesis (GNG) and glycogenolysis (GLY) during prolonged exercise at 30% of VO2max
Effect of exercise intensity on liver glucose output
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