Glucagon

Metabolism

Halflife = 5-10 minutes

Degraded by liver

Actions of glucagon

• Glycogenolysis (in liver only)
• Gluconeogenesis (in liver only)
  * From amino acids
• Lipolysis
• Ketogenesis
• Inotropic effect
  * At large doses
  * Probably because they increase myocardial cAMP
• Stimulates
  * Insulin
  * Pancreatic somatostatin
  * Growth hormone

NB:

• Glucagon does NOT cause glycogenolysis in muscle

Mechanism

• Acts via Gs
  --> Activate adenylyl cyclase
  --> Protein kinase A
  --> Activate phosphorylase
  --> Glycogenolysis
• Or different receptor
  --> Activate phospholipase C
  --> Increase cytoplasmic [Ca2+]
  --> Glycogenolysis

Protein kinase A also

• Decrease concentration of fructose 2,6-diphosphate
  --> Inhibits conversion of F6P to F1,6-P
  --> Increase level of glucose 6-phosphate
  --> Increased release to glucose

Regulation

Stimulator

• Amino acids
  * Glucogenic amino acids, alanine, serine, glycine, systeine, and threonine
• Cortisol
• Exercise
• Infections
• Stress
• Beta-agonist
• Theophylline
• CCK, gastrin

Inhibitors

• Glucose
• Somatostatin
• FFA
• Ketones
• Insulin
• GABA
• Phenytoin
• Alpha-agonist
• Secretin

NB:

• Despite being inhibited by FFA and ketones, glucagon is elevated in DKA

Starvation

• Glucagon secretion increases during starvation
• Reaches peak on the 3rd day
  --> Maximal gluconeogenesis
• Afterwards, level falls as FFA and ketones become major source of energy

Other notes

[WG21:p355]

Glucocorticoids are necessary for glucagon to exert its gluconeogenic actions during fasting
--> role of glucocorticoids is permissive