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 ( )  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 (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 Homeostasis During Exercise Effect of CHO feeding during exercise on glucose homeostasis

CHO metabolism during prolonged exercise (~72% VO 2max ) to exhaustion w/ and w/out CHO feedings (every 20 min) Coyle et al., JAP, hr2 hr3 hr4 hr Placebo CHO RER results

Substrate use during exercise to exhaustion w/ and w/out CHO feeding Decreased muscle glycogen caused increased glucose utilization Coyle et al., JAP, 1986

Hepatic glucose output (HGP) and glucose uptake (Rd) w/ and w/out CHO feedings during prolonged exercise (~70% of VO 2max ) 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

Liver glucose output from gluconeogenesis (GNG) and glycogenolysis (GLY) during prolonged exercise at 30% of VO 2max Effect of exercise intensity on liver glucose output

Effects of Incremental Exercise on Blood Glucose

Liver glucose output from gluconeogenesis (GNG) and glycogenolysis (GLY) during prolonged exercise at 30% of VO 2max Effect of exercise intensity on liver glucose output

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Focus on Research

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