Insulin, Glucagon, and Somatostatin
Describe the physiology of insulin, glucagon and somatostatin.
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.
|Muscle||Increased glucose, amino acid, ketone, and K+ uptake||Increased anabolism, decreased catabolism|
|Fat||Increased glucose (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|
Hyperglycaemia occurs in diabetes due to decreased peripheral utilisation as a 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 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.
|Liver||Glycogenolysis, gluconeogenesis, glucose release, ketone formation|
|Metabolic||Increased metabolic rate, GH release, somatosatin release, insulin release|
Secretion of glucagon is influenced by a number of factors:
|Stimulate Release||Inhibit Release|
|Hypoglycaemia and starvation||Somatostatin|
|Physiological stress: Exercise, infection||Free Fatty Acids|
Somatostatin is a polypeptide hormone that:
- Inhibits secretion of other hormones including:
- Other pancreatic peptides
- May function as a neurotransmitter in the CNS
- 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.