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dc.contributor.authorO'Harte, Finbarr P M
dc.contributor.authorParthsarathy, Vadivel
dc.contributor.authorFlatt, Peter R
dc.date.accessioned2020-04-01T09:59:57Z
dc.date.available2020-04-01T09:59:57Z
dc.date.issued2020-01-03
dc.identifier.citationO'Harte, F.P., Parthsarathy, V. and Flatt, P.R., (2020). 'Chronic apelin analogue administration is more effective than established incretin therapies for alleviating metabolic dysfunction in diabetic db/db mice'. Molecular and Cellular Endocrinology, pp. 1-9.en_US
dc.identifier.pmid31904406
dc.identifier.doi10.1016/j.mce.2019.110695
dc.identifier.urihttp://hdl.handle.net/10545/624636
dc.description.abstractStable apelin-13 peptide analogues have shown promising acute antidiabetic effects in mice with diet-induced obesity diabetes. Here the efficacy of (pGlu)apelin-13 amide (apelin amide) and the acylated analogue (pGlu)(Lys8GluPAL)apelin-13 amide (apelin FA), were examined following chronic administration in db/db mice, a genetic model of degenerative diabetes. Groups of 9-week old male db/db mice (n = 8) received twice daily injections (09:00 and 17:00 h; i.p.) or saline vehicle, apelin amide, apelin FA, or the established incretin therapies, exendin-4(1-39) or liraglutide, all at 25 nmol/kg body weight for 21 days. Control C57BL/6J mice were given saline twice daily. No changes in body weight or food intake were observed with either apelin or liraglutide treatments, but exendin-4 showed a reduction in cumulative food intake (p < 0.01) compared with saline-treated db/db mice. Apelin analogues and incretin mimetics induced sustained improvements of glycaemia (p < 0.05 to p < 0.001, from day 9-21), lowered HbA1c at 21 days (p < 0.05) and raised plasma insulin concentrations. The treatments also improved OGTT and ipGTT with enhanced insulin responses compared with saline-treated control db/db mice (p < 0.05 to p < 0.001). Apelin amide was superior to incretin mimetics in lowering plasma triglycerides by 34% (p < 0.05). Apelin analogues unlike both incretin mimetics reduced pancreatic α-cell area (p < 0.05 to p < 0.01) and all peptide treatments enhanced pancreatic insulin content (p < 0.05 to p < 0.01). In conclusion, longer-term administration of apelin-13 analogues, induced similar and in some respects more effective metabolic improvements than incretin mimetics in db/db mice, providing a viable alternative approach for counteracting metabolic dysfunction for mild and more degenerative forms of the disease.en_US
dc.description.sponsorshipThis work was supported by Invest Northern Ireland, Proof of Concept, Phase III, [PoC518] and the Irish Endocrine Society [small grant 2016], Ireland.en_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S0303720719303971en_US
dc.rightsCopyright © 2020 Elsevier B.V. All rights reserved.
dc.subjectApelin analoguesen_US
dc.subjectDiabetesen_US
dc.subjectIncretin mimeticsen_US
dc.subjectPancreasen_US
dc.subjectTherapyen_US
dc.subjectdb/db miceen_US
dc.titleChronic apelin analogue administration is more effective than established incretin therapies for alleviating metabolic dysfunction in diabetic db/db mice.en_US
dc.typeArticleen_US
dc.identifier.eissn1872-8057
dc.contributor.departmentUniversity of Ulsteren_US
dc.identifier.journalMolecular and cellular endocrinologyen_US
dc.source.journaltitleMolecular and cellular endocrinology
dc.source.volume504
dc.source.beginpage110695
dc.source.endpage
dcterms.dateAccepted219-12-27
dc.author.detail785773en_US
dc.source.countryIreland


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