Insulin lispro is a rapid-acting insulin analogue. Compared to regular human insulin, what structural modification confers its faster onset?

• A Addition of a fatty acid chain to lysine B29, promoting hexamer formation for rapid absorption
• B Deletion of threonine B30 and asparagine B29 residues, producing a truncated molecule with faster clearance
• C Addition of two arginine residues at the C-terminus of the B chain, shifting the isoelectric point
• D Reversal of the B28 proline and B29 lysine residues, disrupting the tendency to form hexamers and allowing rapid dissociation into monomers ✓

Explanation

Regular human insulin self-associates into hexamers at subcutaneous injection sites, requiring slow dissociation into dimers and monomers for absorption — creating a lag time of 30–45 minutes before onset. Insulin lispro has lysine at B28 and proline at B29 (reversed from the natural sequence), disrupting the hydrophobic interactions that stabilize hexamer formation. It exists predominantly as monomers, allowing rapid absorption with onset at 15 minutes and peak at 1–2 hours. Insulin glargine (extended basal) uses the C-terminus arginine modification and different isoelectric point strategy.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.