Insulin detemir

Insulin detemir binds to the insulin receptor (IR), a heterotetrameric protein consisting of two extracellular alpha units and two transmembrane beta units. The binding of insulin to the alpha subunit of IR stimulates the tyrosine kinase activity intrinsic to the beta subunit of the receptor. The bound receptor autophosphorylates and phosphorylates numerous intracellular substrates such as insulin receptor substrates (IRS) proteins, Cbl, APS, Shc and Gab 1. Activation of these proteins leads to the activation of downstream signalling molecules including PI3 kinase and Akt. Akt regulates the activity of glucose transporter 4 (GLUT4) and protein kinase C (PKC), both of which play critical roles in metabolism and catabolism.

Insulin detemir’s long duration of action appears to be a result of slow systemic absorption from the injection site and delayed distribution to target tissues. The myristic acid side chain on insulin detemir increases self-association and gives it a high binding affinity to serum albumin. These features slow its distribution into target tissues and prolong its duration of action.