Insulin lispro differs from regular insulin in its rapid onset. The structural modification causing faster absorption from subcutaneous tissue is:
- A Substitution of proline at B28 with lysine, and lysine at B29 with proline, reducing self-association into hexamers ✓
- B Addition of two arginine residues at the C-terminus of the B chain, shifting isoelectric point
- C Zinc removal from the insulin hexamer to maintain monomeric form
- D PEGylation of the insulin molecule to increase solubility
Correct answer: A. Substitution of proline at B28 with lysine, and lysine at B29 with proline, reducing self-association into hexamers
Explanation
Regular insulin at the B26-B30 region forms strong intermolecular contacts promoting hexamer and dimer formation; lispro reverses positions B28 (Pro→Lys) and B29 (Lys→Pro), sterically disrupting hexamer self-association, so lispro exists predominantly as monomers/dimers at therapeutic concentrations. Monomers are absorbed ~2-fold faster than hexamers from subcutaneous tissue, producing onset within 15 minutes. Glargine uses the arginine addition (option B) for prolonged action by shifting isoelectric point.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.