Characterisation of insulin analogues therapeutically available to patients

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dc.authorid0000-0002-0335-2162en_US
dc.authorid0000-0002-5870-1446en_US
dc.authorid0000-0002-4706-9916en_US
dc.authorid0000-0002-7798-9692en_US
dc.authorid0000-0003-2861-2458en_US
dc.authorid0000-0002-7050-4082
dc.contributor.authorAdams, Gary G.
dc.contributor.authorMeal, Andrew
dc.contributor.authorMorgan, Paul S.
dc.contributor.authorAlzahrani, Qushmua E.
dc.contributor.authorZobel, Hanne
dc.contributor.authorLithgo, Ryan
dc.contributor.authorKök, Mehmet Şamil
dc.date.accessioned2021-06-23T19:49:52Z
dc.date.available2021-06-23T19:49:52Z
dc.date.issued2018
dc.departmentBAİBÜ, Mühendislik Fakültesi, Gıda Mühendisliği Bölümüen_US
dc.description.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.en_US
dc.identifier.doi10.1371/journal.pone.0195010
dc.identifier.issn1932-6203
dc.identifier.issue3en_US
dc.identifier.pmid29596514en_US
dc.identifier.scopus2-s2.0-85044987371en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0195010
dc.identifier.urihttps://hdl.handle.net/20.500.12491/9638
dc.identifier.volume13en_US
dc.identifier.wosWOS:000428630000066en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKök, Mehmet Şamil
dc.language.isoenen_US
dc.publisherPublic Library Scienceen_US
dc.relation.ispartofPlos Oneen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectInsulin Analoguesen_US
dc.titleCharacterisation of insulin analogues therapeutically available to patientsen_US
dc.typeArticleen_US

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