Characterisation of insulin analogues therapeutically available to patients
AuthorsAdams, Gary G.
Morgan, Paul S.
Alzahrani, Qushmua E.
Kok, M. Samil
Besong, David T. M.
Jiwani, Shahwar I.
Harding, Stephen E.
Gillis, Richard B.
KAUST DepartmentFunctional Nanomaterials Lab, King Abdullah University of Science and Technology (KAUST), Thuwal, Kingdom of Saudi Arabia.
MetadataShow full item record
AbstractThe 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.
CitationAdams GG, Meal A, Morgan PS, Alzahrani QE, Zobel H, et al. (2018) Characterisation of insulin analogues therapeutically available to patients. PLOS ONE 13: e0195010. Available: http://dx.doi.org/10.1371/journal.pone.0195010.
SponsorsDr. Gary Adams is a non-executive director for the Independent Diabetes Trust and accepts no remuneration for the role. Dr’s Hanne Zobel and Simon Ballance are employees of Nofima AS, however this organisation did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors’ salaries and research materials. The specific roles of these authors are articulated in the ‘author contributions’ section.
PublisherPublic Library of Science (PLoS)
Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Glargine and degludec: Solution behaviour of higher dose synthetic insulins.
- Authors: Adams GG, Alzahrani Q, Jiwani SI, Meal A, Morgan PS, Coffey F, Kok S, Rowe AJ, Harding SE, Chayen N, Gillis RB
- Issue date: 2017 Aug 4
- Investigation of the Physico-Chemical Properties that Enable Co-Formulation of Basal Insulin Degludec with Fast-Acting Insulin Aspart.
- Authors: Havelund S, Ribel U, Hubálek F, Hoeg-Jensen T, Wahlund PO, Jonassen I
- Issue date: 2015 Jul
- Effects of phenol and meta-cresol depletion on insulin analog stability at physiological temperature.
- Authors: Teska BM, Alarcón J, Pettis RJ, Randolph TW, Carpenter JF
- Issue date: 2014 Aug
- Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus.
- Authors: Atkin S, Javed Z, Fulcher G
- Issue date: 2015 Nov
- Safety of insulin analogues as compared with human insulin in pregnancy.
- Authors: Toledano Y, Hadar E, Hod M
- Issue date: 2016 Jul