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dc.contributor.authorO'Harte, Finbarr P M
dc.contributor.authorParthsarathy, Vadivel
dc.contributor.authorHogg, Christopher
dc.contributor.authorFlatt, Peter R
dc.date.accessioned2020-04-01T09:21:03Z
dc.date.available2020-04-01T09:21:03Z
dc.date.issued2017-10-04
dc.identifier.citationO'Harte, F., Parthsarathy, V., Hogg, C., and Flatt, P. (2017). 'Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties'. Biochemical Pharmacology, 146 . pp. 165-173.en_US
dc.identifier.pmid28987595
dc.identifier.doi10.1016/j.bcp.2017.10.002
dc.identifier.urihttp://hdl.handle.net/10545/624634
dc.description.abstractThe adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, Lys8GluPAL)apelin-13 amide, pGlu(Lys8GluPAL)apelin-13 amide, Lys8GluPAL(Tyr13)apelin-13 and Lys8GluPAL(Val13)apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys8GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p < .001). (Lys8GluPAL)apelin-13 amide (1.9-fold) and Lys8GluPAL(Tyr13)apelin-13 (1.7-fold) were less effective, whereas Lys8GluPAL(Val13)apelin-13 had an inhibitory effect on insulin secretion. Similarly, pGlu(Lys8GluPAL)apelin-13 amide was most potent in increasing beta-cell intracellular Ca2+ concentrations (1.8-fold, p < .001) and increasing glucose uptake in 3T3-L1 adipocytes (2.3-fold, p < .01). Persistent biological action was observed with both pGlu(Lys8GluPAL)apelin-13 amide and (Lys8GluPAL)apelin-13 amide significantly reducing blood glucose (39-43%, p < .01) and enhancing insulin secretion (43-56%, p < .001) during glucose tolerance tests in diet-induced obese mice. pGlu(Lys8GluPAL)apelin-13 amide and (Lys8GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys8GluPAL(Val13)apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes.en_US
dc.description.sponsorshipThese studies were supported by a PhD research studentship from Northern Ireland Department of Education and Learning (DEL) to C.H. as well as SAAD Corporation funding and Ulster University Research Strategy (PoP) funding.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.urlhttp://uir.ulster.ac.uk/38767/en_US
dc.relation.urlhttps://www.sciencedirect.com/science/article/abs/pii/S0006295217306160?via%3Dihuben_US
dc.rightsCopyright © 2017 Elsevier Inc. All rights reserved.
dc.subjectAdipokineen_US
dc.subjectApelin-13en_US
dc.subjectFeedingen_US
dc.subjectGlucose homeostasis insulin releaseen_US
dc.subjectGlucose uptakeen_US
dc.subjectObesityen_US
dc.subjectType 2 diabetesen_US
dc.titleAcylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic propertiesen_US
dc.typeArticleen_US
dc.identifier.eissn1873-2968
dc.contributor.departmentUniversity of Ulsteren_US
dc.identifier.journalBiochemical pharmacologyen_US
dc.source.journaltitleBiochemical pharmacology
dc.source.volume146
dc.source.beginpage165
dc.source.endpage173
dcterms.dateAccepted2017-10-02
dc.author.detail785773en_US
dc.source.countryEngland


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