Glucose Homeostasis

2. 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)

3. 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

4. Glucose ProductionDuring Exercise

5. 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]

6. Cori Cycle

7. 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

8. 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

9. Glucose-alanine cycleLeucine is 1° BCAA that provides N for alanine formation. This model may not operate when glucose & glycogen is low leucine

10. Interrelationship of leucine catabolism and alanine formationRate of appearance (Ra) of alanine (a) and leucine N transfer to alanine (b) at rest and during exerciseWolf et al., 1982, 1984

11. 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

12. 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

13. 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

14. 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

15. Glucose HomeostasisDuring Exercise Effect of CHO feeding during exercise on glucose homeostasis

16. 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

17. 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

18. Effects of Prolonged Exercise on Blood Glucose

26. Effect of exercise intensity on liver glucose output Liver glucose output from gluconeogenesis (GNG) and glycogenolysis (GLY) during prolonged exercise at 30% of VO2max

27. Effects of Incremental Exercise on Blood Glucose

31. 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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