Insulin degludec has a duration of action exceeding 42 hours. What structural modification of native insulin accounts for this ultra-long action?
- A Addition of a polyethylene glycol (PEGylation) to delay renal clearance
- B Removal of ThrB30 and attachment of a C16 fatty acid chain to LysB29 via a glutamic acid spacer, enabling multi-hexamer formation and gradual absorption ✓
- C Substitution of HisB10 with Asp, reducing zinc-binding and preventing hexamer formation
- D Addition of two extra arginines at the B-chain C-terminus and substitution of Asn at A21 with Gly, shifting the isoelectric point
Correct answer: B. Removal of ThrB30 and attachment of a C16 fatty acid chain to LysB29 via a glutamic acid spacer, enabling multi-hexamer formation and gradual absorption
Explanation
Insulin degludec has ThrB30 deleted and a C16 fatty diacid chain attached to LysB29 via a gamma-glutamic acid linker. In the subcutaneous depot, it self-assembles into large soluble multi-hexamer chains held together by zinc and fatty acid interactions. These gradually dissociate and absorb as monomers, producing a flat, peakless, >42-hour action profile. Option D describes insulin glargine's modifications.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.