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, increased to 0.146 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 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 is a polypeptide hormone that:

  • Inhibits secretion pancreatic polypeptides including insulin and glucagon
  • May function as a neurotransmitter in the CNS


  1. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.
  2. Peck TE, Hill SA. Pharmacology for Anaesthesia and Intensive Care. 4th Ed. Cambridge University Press. 2014.
Last updated 2021-07-14

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