1. Hormonal regulation of metabolism

2. Hormones that affect energy metabolism
Message
insulin
glucose and amino acids available, more substrates on the way
glucagon
glucose and amino acids in short supply, need to mobilize internal reserves
epinephrine
prepare for imminent sharp rise in substrate demand
glucocorticoids
prepare for extended period of high demand
thyroid hormones
increase basal metabolic rate

3. Langerhans’ islets in the pancreas produce insulin and glucagon

4. A little bit of history: The purification of insulin—the problem

5. The purification of insulin—Banting’s solution

6. Historical side note: Norman Bethune, Banting’s famous classmate

7. Structure of insulin and its precursors (1)

8. Structure of insulin and its precursors (2)

9. Sequences of human, swine, and bovine insulins

10. Insulin secretion in the β-cell is controlled by glucose and triggered by membrane depolarization

11. The sulfonylurea receptor controls an associated potassium channel

12. KATP channels also regulate the tone of smooth muscle cells

13. Tolbutamide promotes closing of the KATP channel

14. The insulin receptor is a receptor tyrosine kinase

15. Insulin receptor first phosphorylates itself and then a number of insulin receptor substrate proteins

16. Insulin effects on glycogen synthesis

17. The role of insulin in glucose transport
Active transport
Facilitated transport
insulin-independent
small intestine, kidney tubules
brain, β-cells, red blood cells, cornea and lens of the eye
insulin-dependent
never
muscle, fat, most other tissues

18. Insulin promotes glucose uptake by increasing the surface exposure of GLUT 4 transporters

19. Transcriptional regulation by insulin

20. Other hormones

21. Glucagon and epinephrine act via G-protein-coupled receptors

22. The glucagon and epinephrine receptors activate adenylate cyclase and protein kinase A

23. Metabolic effects of protein kinase A
Target
Effect
Metabolic consequence
glycogen synthase ↓
glucose is not locked up in glycogen, remains available
phosphorylase kinase ↑
phosphorylase is activated, glucose is released from glycogen storage
PFK-2 / Fructose-2,6-bisphosphatase
↓ / ↑
Fructose-2,6-bisphosphate drops; glycolysis is inhibited, gluconeogenesis is activated
hormone-sensitive lipase
fatty acids are mobilized for β-oxidation and ketogenesis

24. Glucocorticoids and thyroid hormones act on nuclear hormone receptors to activate transcription

25. DNA binding by thyroid hormone receptors

26. Thyroid hormones induce respiratory chain uncoupling proteins

27. Metabolic effects of glucocorticoid hormones
induction of enzymes for glycogen synthesis, glycogen breakdown, as well as gluconeogenesis
induction of enzymes for protein breakdown, which supplies substrates for gluconeogenesis
induction of adrenergic receptors
…overall, glucocorticoids increase blood glucose

28. Glucocorticoid receptor agonists and antagonists

29. Control of food intake by leptin