Glargine and degludec: solution behaviour of higher dose synthetic insulins

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...

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Main Authors: 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.
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Published: Nature Publishing Group 2017
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Online Access:https://eprints.nottingham.ac.uk/44848/
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author 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.
author_facet 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.
author_sort Adams, Gary G.
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-448482020-05-04T18:58:53Z https://eprints.nottingham.ac.uk/44848/ 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. 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. Nature Publishing Group 2017-08-04 Article PeerReviewed 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 and Gillis, Richard B. (2017) Glargine and degludec: solution behaviour of higher dose synthetic insulins. Scientific Reports, 7 (1). 7287/1-7287/11. ISSN 2045-2322 Diabetes complications; Protein delivery https://www.nature.com/articles/s41598-017-06642-w doi:10.1038/s41598-017-06642-w doi:10.1038/s41598-017-06642-w
spellingShingle Diabetes complications; Protein delivery
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.
Glargine and degludec: solution behaviour of higher dose synthetic insulins
title Glargine and degludec: solution behaviour of higher dose synthetic insulins
title_full Glargine and degludec: solution behaviour of higher dose synthetic insulins
title_fullStr Glargine and degludec: solution behaviour of higher dose synthetic insulins
title_full_unstemmed Glargine and degludec: solution behaviour of higher dose synthetic insulins
title_short Glargine and degludec: solution behaviour of higher dose synthetic insulins
title_sort glargine and degludec: solution behaviour of higher dose synthetic insulins
topic Diabetes complications; Protein delivery
url https://eprints.nottingham.ac.uk/44848/
https://eprints.nottingham.ac.uk/44848/
https://eprints.nottingham.ac.uk/44848/