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Utilisation of the isobole methodology to study dietary peptide-drug and peptide-peptide interactive effects on dipeptidyl peptidase IV (DPP-IV) inhibition

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dc.contributor.author Nongonierma, Alice B.
dc.contributor.author Fitzgerald, Richard J.
dc.date.accessioned 2017-04-26T10:50:55Z
dc.date.available 2017-04-26T10:50:55Z
dc.date.issued 2015
dc.identifier.uri http://hdl.handle.net/10344/5728
dc.description peer-reviewed en_US
dc.description.abstract Inhibition of dipeptidyl peptidase-IV (DPP-IV) is used as a means to regulate post-prandial serum glucose in type 2 diabetics. The effect of drug (Sitagliptin®)/peptide and binary peptide mixtures on DPP-IV inhibition was studied using an isobole approach. Five peptides (Ile-Pro-Ile-Gln-Tyr, Trp-Lys, Trp-Pro, Trp-Arg and Trp-Leu), having DPP-IV half maximum inhibitory concentration values (IC₅₀)<60 μM and reported to act through different inhibition mechanisms, were investigated. The dose response relationship of Sitagliptin : peptide (1:0, 0:1, 1:852, 1:426 and 1:1704 on a molar basis) and binary Ile-Pro-Ile-Gln-Tyr : peptide (1:0, 0:1, 1:1, 1:2 and 2:1 on a molar basis) mixtures for DPP-IV inhibition was characterised. Isobolographic analysis showed, in most instances, an additive effect on DPP-IV inhibition. However, a synergistic effect was observed with two Sitagliptin:Ile-Pro-Ile-Gln-Tyr (1:426 and 1:852) mixtures and an antagonistic effect was seen with one Sitagliptin : Trp-Pro (1:852) mixture, and three binary peptide mixtures (Ile-Pro-Ile-Gln-Tyr : Trp-Lys (1:1 and 2:1) and Ile-Pro-Ile-Gln-Tyr:Trp-Leu (1:2)). The results show that Sitagliptin and food protein-derived peptides can interact, thereby enhancing overall DPP-IV inhibition. Combination of Sitagliptin with food protein-derived peptides may help in reducing drug dosage and possible associated side-effects. en_US
dc.language.iso eng en_US
dc.publisher Royal Society of Chemistry en_US
dc.relation.ispartofseries Food and Function;6 (1), pp. 313-20
dc.relation.uri http://dx.doi.org/10.1039/c4fo00883a
dc.subject induced diabetic-rats en_US
dc.subject beta-lactoglobulin en_US
dc.subject whey proteins en_US
dc.subject amino-acids en_US
dc.title Utilisation of the isobole methodology to study dietary peptide-drug and peptide-peptide interactive effects on dipeptidyl peptidase IV (DPP-IV) inhibition en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.date.updated 2017-04-10T18:22:11Z
dc.description.version ACCEPTED
dc.identifier.doi 10.1039/c4fo00883a
dc.contributor.sponsor EI en_US
dc.relation.projectid TC2013-0001 en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US
dc.internal.rssid 1577246
dc.internal.copyrightchecked Yes
dc.identifier.journaltitle Food & Function
dc.description.status peer-reviewed


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