A patient with type 1 diabetes is switched from regular human insulin to insulin lispro for mealtime coverage. The faster onset of lispro compared to regular insulin is primarily due to which structural difference?
- A Lispro has reversed B28 proline and B29 lysine, reducing self-association into dimers and hexamers ✓
- B Lispro lacks the C-peptide that delays absorption of regular insulin
- C Lispro is formulated with zinc-free buffer, preventing hexamer formation
- D Lispro has a fatty acid side chain that accelerates subcutaneous absorption
Correct answer: A. Lispro has reversed B28 proline and B29 lysine, reducing self-association into dimers and hexamers
Explanation
Insulin lispro has reversed positions of proline at A28 and lysine at A29. This single change reduces the tendency to self-associate into dimers and hexamers after subcutaneous injection, so it is absorbed as monomers within 15 minutes. Regular insulin forms stable hexamers that must dissociate before absorption, giving a slower 30 to 60 minute onset.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
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