Insulin, Glucagon, and Somatostatin
Describe the physiology of insulin, glucagon and somatostatin.
Insulin
Insulin is a polypeptide hormone, and is:
- Synthesised from proinsulin in the rough endoplasmic reticulum of B cells in the Islets of Langerhans
- Excreted via exocytosis in response to an increase in intracellular Ca2+
- Minimally protein bound with a tiny volume of distribution
VD 0.075 L.kg-1, increased to 0.146 L.kg-1 in diabetics. - Metabolised in liver, muscle, and kidney by glutathione insulin transhydrogenase, with renal elimination of inactive metabolites
Circulatory half-life of ~5min.
Actions of Insulin
Insulin binds to a specific insulin receptor (a membrane-spanning protein composed of α and β subunits) on the cell membrane. The complex is internalised, and its effects are mediated by tyrosine kinase.
| Seconds | Minutes | Hours | |
|---|---|---|---|
| Muscle | Increased glucose (active transport via GLUT4), amino acid, ketone, and K+ uptake | Increased anabolism, decreased catabolism | |
| Fat | Increased glucose (active transport via GLUT4), amino acid, and K+ uptake | Increased glycerol phosphate synthesis | Increased fatty acid synthesis |
| Liver | Decreased: gluconeogenesis, ketogenesis. Increased: glycogen synthesis, glycolysis, protein synthesis, lipid synthesis |
||
| General | Increased cell growth |
Note that cells do not require insulin to take up glucose. GLUT1 receptors allow free entry of glucose into cells via facilitated diffusion; i.e. Metabolism drives glucose uptake. Active transport of insulin in fat and muscle leads to triglyceride and glycogen production, respectively. Incidentally, the hyperglycaemia seen in diabetes is due uninhibited hepatic gluconeogenesis, and the acidosis due to uninhibited hepatic ketogenesis.
Glucose Tolerance
Hyperglycaemia occurs in diabetes due to decreased peripheral utilisation as glucose uptake is reduced due to absence of or resistance to insulin. In addition, the suppressive effect of insulin on hepatic gluconeogenesis is absent or reduced.
Glucagon
Glucagon is a polypeptide hormone, and is:
- Synthesised in the A cells of the pancreas
- Has a circulating half-life of ~5min
- Metabolised predominantly in the liver
Secreted directly into the portal vein, and undergoes first-pass metabolism resulting in low circulating levels.
| System | Effect |
|---|---|
| Liver | Glycogenolysis, gluconeogenesis, glucose release, ketone formation |
| CVS | Inotropy |
| Fat | Lipolysis |
| Metabolic | Increased metabolic rate, GH release, somatostatin release, insulin release |
Secretion of glucagon is influenced by a number of factors:
| Stimulate Release | Inhibit Release |
|---|---|
| Hypoglycaemia and starvation | Somatostatin |
| Amino acids | Secretin |
| Physiological stress: Exercise, infection | Free Fatty Acids |
| β-agonists | α-agonists |
| Cortisol | Insulin |
| ACh | Ketones |
| Theophylline | GABA |
Somatostatin
Somatostatin is a polypeptide hormone that:
- Inhibits secretion pancreatic polypeptides including insulin and glucagon
- May function as a neurotransmitter in the CNS
References
- Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.
- Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.