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 ProductionDuring 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 (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

Glucose HomeostasisDuring 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

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

Effects of Incremental Exercise on Blood Glucose

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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