Glargine and degludec: Solution behaviour of higher dose synthetic insulins

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 pers...

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Autores principales:	Gary G. Adams, Qushmua Alzahrani, Shahwar I. Jiwani, Andrew Meal, Paul S. Morgan, Frank Coffey, Samil Kok, Arthur J. Rowe, Stephen E. Harding, Naomi Chayen, Richard B. Gillis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b78d16e655964b44a202114d783230a1
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spelling	oai:doaj.org-article:b78d16e655964b44a202114d783230a12021-12-02T12:32:32ZGlargine and degludec: Solution behaviour of higher dose synthetic insulins10.1038/s41598-017-06642-w2045-2322https://doaj.org/article/b78d16e655964b44a202114d783230a12017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06642-whttps://doaj.org/toc/2045-2322Abstract 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.Gary G. AdamsQushmua AlzahraniShahwar I. JiwaniAndrew MealPaul S. MorganFrank CoffeySamil KokArthur J. RoweStephen E. HardingNaomi ChayenRichard B. GillisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gary G. Adams Qushmua Alzahrani Shahwar I. Jiwani Andrew Meal Paul S. Morgan Frank Coffey Samil Kok Arthur J. Rowe Stephen E. Harding Naomi Chayen Richard B. Gillis Glargine and degludec: Solution behaviour of higher dose synthetic insulins
description	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.
format	article
author	Gary G. Adams Qushmua Alzahrani Shahwar I. Jiwani Andrew Meal Paul S. Morgan Frank Coffey Samil Kok Arthur J. Rowe Stephen E. Harding Naomi Chayen Richard B. Gillis
author_facet	Gary G. Adams Qushmua Alzahrani Shahwar I. Jiwani Andrew Meal Paul S. Morgan Frank Coffey Samil Kok Arthur J. Rowe Stephen E. Harding Naomi Chayen Richard B. Gillis
author_sort	Gary G. Adams
title	Glargine and degludec: Solution behaviour of higher dose synthetic insulins
title_short	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_sort	glargine and degludec: solution behaviour of higher dose synthetic insulins
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b78d16e655964b44a202114d783230a1
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Glargine and degludec: Solution behaviour of higher dose synthetic insulins

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