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