Neutral human insulin
(Actrapid, Humulin)

Class Insulin
Chemistry

Peptide hormone: Two chains, B (30 amino acids) and A (21 amino acids), with amino acids labelled by chain letter and number.

Routes of administration

IV or subcutaneously

Absorption

Essenially zero oral bioavailability. Absorbed from subcutaneous depot: onset of clinical effect is within about 30-60 min

Solubility

In low concentrations, present in monomeric form and is highly soluble. In high concentrations, undergoes oligomerisation, and becomes insoluble, with a pKA of 5.4

Distribution

VOD= 0.44 L/kg; minimally protein-bound

Metabolism

Over 50% metabolism by the liver, 30% by the proximal tubule in the kdiney, the rest by skeletal muscle and adipose tissue. Ligand/receptor complex is endocytosed and degraded after it binds its receptor.

Elimination

Only 1% of the free drug is eliminated in the kidney

Time course of action

Onset of effect = 30-60 min, peak activity at 2-3 hrs, duration of action apporoximately 6-10 hrs

Target receptor

Insulin receptor, a transmembrane receptor with an intracellular tyrosine kinase domai, which uses the PI3K secondary messenger pathway for intracellular signalling

Mechanism of action

Increases the exocytosis and cell surface expression of GLUT4 transport proteins, which results in the uptake of glucose into insulin-sensitive tissues. Also multiple metabolic effects: decreased glycogenolysis and increased glycogen synthesis in the liver, decreased free fatty acid mobilisation by fatty tissue, increased lipoprotein lipase activity, decreased protein catabolism, positive inotrpic effects, and decreased releae of glucagon

Clinical effects
  • Binds to transmembrane receptors with intracellular tyrosine kinase domain
  • Activates mechanisms to translocate GLUT4 glucose transporter proteins to the cell membrane, to increase cellular glucose uptake
  • Also multiple metabolic effects: 
    • decreased hepatic glycogenolysis
    • increased hepatic glycogen synthesis
    • decreased free fatty acid mobilisation by fatty tissue
    • increased lipoprotein lipase activity
    • decreased protein catabolism
    • positive inotropic effects
    • decreased release of glucagon
Literature reference

Owens, 1986

CICM details of understanding Level 1
Mentioned around Deranged Physiology
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