Characterisation of insulin analogues therapeutically available to patients
The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51022/ |
| _version_ | 1848798394843136000 |
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| author | Adams, Gary G. Meal, Andrew Morgan, Paul S. Alzahrani, Qushmua E. Zobel, Hanne Lithgo, Ryan Kok, M. Samil Besong, David T.M. Jiwani, Shahwar I. Ballance, Simon Harding, Stephen E. Gillis, Richard B. Chayen, Naomi |
| author_facet | Adams, Gary G. Meal, Andrew Morgan, Paul S. Alzahrani, Qushmua E. Zobel, Hanne Lithgo, Ryan Kok, M. Samil Besong, David T.M. Jiwani, Shahwar I. Ballance, Simon Harding, Stephen E. Gillis, Richard B. Chayen, Naomi |
| author_sort | Adams, Gary G. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein. |
| first_indexed | 2025-11-14T20:19:05Z |
| format | Article |
| id | nottingham-51022 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:19:05Z |
| publishDate | 2018 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-510222020-05-08T09:15:32Z https://eprints.nottingham.ac.uk/51022/ Characterisation of insulin analogues therapeutically available to patients Adams, Gary G. Meal, Andrew Morgan, Paul S. Alzahrani, Qushmua E. Zobel, Hanne Lithgo, Ryan Kok, M. Samil Besong, David T.M. Jiwani, Shahwar I. Ballance, Simon Harding, Stephen E. Gillis, Richard B. Chayen, Naomi The structure and function of clinical dosage insulin and its analogues were assessed. This included ‘native insulins’ (human recombinant, bovine, porcine), ‘fast-acting analogues’ (aspart, glulisine, lispro) and ‘slow-acting analogues’ (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein. Public Library of Science 2018-03-29 Article PeerReviewed application/pdf en cc_by https://eprints.nottingham.ac.uk/51022/1/journal.pone.0195010GA.pdf Adams, Gary G., Meal, Andrew, Morgan, Paul S., Alzahrani, Qushmua E., Zobel, Hanne, Lithgo, Ryan, Kok, M. Samil, Besong, David T.M., Jiwani, Shahwar I., Ballance, Simon, Harding, Stephen E., Gillis, Richard B. and Chayen, Naomi (2018) Characterisation of insulin analogues therapeutically available to patients. PLoS ONE, 13 (3). e0195010/1-e0195010/17. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195010 doi:10.1371/journal.pone.0195010 doi:10.1371/journal.pone.0195010 |
| spellingShingle | Adams, Gary G. Meal, Andrew Morgan, Paul S. Alzahrani, Qushmua E. Zobel, Hanne Lithgo, Ryan Kok, M. Samil Besong, David T.M. Jiwani, Shahwar I. Ballance, Simon Harding, Stephen E. Gillis, Richard B. Chayen, Naomi Characterisation of insulin analogues therapeutically available to patients |
| title | Characterisation of insulin analogues therapeutically available to patients |
| title_full | Characterisation of insulin analogues therapeutically available to patients |
| title_fullStr | Characterisation of insulin analogues therapeutically available to patients |
| title_full_unstemmed | Characterisation of insulin analogues therapeutically available to patients |
| title_short | Characterisation of insulin analogues therapeutically available to patients |
| title_sort | characterisation of insulin analogues therapeutically available to patients |
| url | https://eprints.nottingham.ac.uk/51022/ https://eprints.nottingham.ac.uk/51022/ https://eprints.nottingham.ac.uk/51022/ |