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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.

Authors

Qushmua Alzahrani

ANDY MEAL andy.meal@nottingham.ac.uk
Assistant Professor

Paul S. Morgan

FRANK COFFEY frank.coffey@nottingham.ac.uk
Clinical Consultant To The Postgraduateclinical Skills Prog

Samil Kok

Arthur J. Rowe

Naomi Chayen



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., …Gillis, R. B. (2017). Glargine and degludec: solution behaviour of higher dose synthetic insulins. Scientific Reports, 7(1), 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
Print ISSN 2045-2322
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 http://eprints.nottingham.ac.uk/id/eprint/44848
Publisher URL https://www.nature.com/articles/s41598-017-06642-w
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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