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Subsequent analyses included assessment of food intake and glucose tolerance in normal mice and rats, as well as high\u2010fat\u2010fed (HFF) mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Enzymatic stability of all ELA peptides was initially confirmed in murine plasma. All peptides significantly augmented insulin secretion from BRIN\u2010BD11 cells and isolated islets, linked to engagement of both GLP\u20101 and apelin receptors, with ELA, ELA\u2010Lys\n                      <jats:sup>12<\/jats:sup>\n                      (\u03b3GluPal) and ELA\u2010Lys\n                      <jats:sup>38<\/jats:sup>\n                      (\u03b3GluPal) being particularly effective. These hybrid peptides also enhanced beta\u2010cell proliferation and reduced cytokine\u2010induced apoptosis. Assessment of effects on feeding behaviour revealed substantial reductions of food intake by ELA, durable for 42\u2009h. Peptide acylation extended the duration of appetite suppressive actions to 63\u2009h. As with in\u00a0vitro actions, appetite regulatory effects were dependent on engagement of both the GLP\u20101 and apelin receptors. Studies in rats suggested that ELA\u2010induced inhibition of food intake was not linked to malaise. All peptides significantly improved glucose tolerance in lean and HFF mice, indicating enhanced insulin action and glycaemic control. Acylation extended the duration of glucose\u2010lowering benefits up to 21\u2009h. Effects of ELA on glucose homeostasis appeared to be more reliant on GLP\u20101, rather than apelin, receptors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These studies highlight the clear therapeutic applicability of rationally designed GLP\u20101\/apelin hybrid molecules for the treatment of obesity and T2DM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70647","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T09:27:22Z","timestamp":1773653242000},"page":"4706-4717","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unimolecular\n                    <scp>GLP<\/scp>\n                    \u20101\/Apelin Hybrid Peptides Cause Prominent Appetite Suppression, as Well as Enhancing Insulin Secretion, Beta\u2010Cell Survival and Glycaemic Regulation"],"prefix":"10.1111","volume":"28","author":[{"given":"Ananyaa","family":"Sridhar","sequence":"first","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences Ulster University  Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan S.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences Ulster University  Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L.","family":"Craig","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences Ulster University  Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Krason\u2010Kidzinska","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences Ulster University  Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-964X","authenticated-orcid":false,"given":"Nigel","family":"Irwin","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences Ulster University  Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7199-4239","authenticated-orcid":false,"given":"Finbarr P. 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