What question did this study set out to answer?

To identify the structural requirements and molecular protraction mechanism of B29-fatty acid acylated basal insulin analogues, specifically insulin degludec.

April 6, 2012Pharmaceutical ResearchOpen Access

Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

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Authors

IJInge JonassenUniversity of Bergen SHSvend HavelundNovo Nordisk (Denmark)THThomas Høeg-JensenNovo Nordisk (Denmark)

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Implication

Biophysical analysis reveals that insulin degludec forms soluble multihexamer filaments upon subcutaneous injection conditions, indicating a mechanism for steady ultra-long basal action.

Key Points

To identify the structural requirements and molecular protraction mechanism of B29-fatty acid acylated basal insulin analogues, specifically insulin degludec.
Assessed self-association, molecular masses, and hexamer conformations using size exclusion chromatography coupled with UV or multi-angle light scattering and dynamic light scattering.
Tracked conformational transitions using circular dichroism spectroscopy under varying phenol and zinc concentrations to mimic pharmaceutical formulation versus post-injection subcutaneous tissue.
Depletion of phenol induced insulin degludec to transition from dihexamers in a T3R3 conformation into stable, high-molecular-weight multihexamer filaments in a T6 conformation.
Subsequent depletion of zinc disassembled the multihexamers, and weak dimeric association promoted rapid release of individual insulin monomers.

Cite This Study

Jonassen et al. (2012) studied this question.

synapsesocial.com/papers/6a71340253da1ffdb507b699 https://doi.org/10.1007/s11095-012-0739-z

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Implication

Biophysical analysis reveals that insulin degludec forms soluble multihexamer filaments upon subcutaneous injection conditions, indicating a mechanism for steady ultra-long basal action.

Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

Discussion

Member takes

Implication

Key Points

Cite This Study

Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

Discussion

Member takes

Implication

Key Points

Cite This Study

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