Glargine and degludec: solution behaviour of higher dose synthetic insulins

Adams, Gary G.; Alzahrani, Qushmua; Jiwani, Shahwar I.; Meal, Andrew; Morgan, Paul S.; Coffey, Frank; Kok, Samil; Rowe, Arthur J.; Harding, Stephen E.; Chayen, Naomi; Gillis, Richard B.

Abstract

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers (“multi-hexamerisation”). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24–40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes.

Citation

Adams, G. G., Alzahrani, Q., Jiwani, S. I., Meal, A., Morgan, P. S., Coffey, F., Kok, S., Rowe, A. J., Harding, S. E., Chayen, N., & Gillis, R. B. (2017). Glargine and degludec: solution behaviour of higher dose synthetic insulins. Scientific Reports, 7(1), Article 7287. https://doi.org/10.1038/s41598-017-06642-w

• Journal Article Type: Article
• Acceptance Date: Jun 15, 2017
• Online Publication Date: Aug 4, 2017
• Publication Date: 2017-12
• Deposit Date: Aug 11, 2017
• Publicly Available Date: Aug 11, 2017
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 1
• Article Number: 7287
• DOI: https://doi.org/10.1038/s41598-017-06642-w
• Keywords: Diabetes complications; Protein delivery
• Public URL: https://nottingham-repository.worktribe.com/output/876096
• Publisher URL: https://www.nature.com/articles/s41598-017-06642-w
• Contract Date: Aug 11, 2017