{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:05:27Z","timestamp":1790139927991,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department for the Economy, Northern Ireland","id":[{"id":"https:\/\/ror.org\/0161w0r98","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0161w0r98","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ulster University Proof of Principle funding","award":["U770"],"award-info":[{"award-number":["U770"]}]},{"award":["U770"],"award-info":[{"award-number":["U770"]}],"id":[{"id":"https:\/\/ror.org\/01yp9g959","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objective: Kisspeptin peptides are being increasingly recognised as regulators of metabolism, but whether these actions differ depending on peptide isoform remains unclear. Methods: The current study compared the enzymatic stability and biological effects of kisspeptin-14 (KP-14), kisspeptin-13 (KP-13) and kisspeptin-10 (KP-10) on beta-cell health and function, glucose homeostasis and appetite. Peptide stability was assessed in murine plasma and, following confirmation of KISS1R expression in BRIN-BD11 beta-cells, actions on insulin secretion, beta-cell proliferation and apoptosis were investigated, with additional secretory studies in isolated murine islets. Metabolic effects of KP-14, KP-13 and KP-10 were subsequently evaluated in healthy male and female mice. Results: KP-14 was resistant to plasma degradation, whereas KP-13 and KP-10 underwent N-terminal proteolysis, with KP-13 degradation generating KP-10 amongst other fragment peptides. The kisspeptin peptides exerted modest direct effects on insulin secretion from BRIN-BD11 cells, with KP-13 being the most efficacious, a bioactivity profile that was confirmed in islets. In addition, KP-13 significantly enhanced beta-cell proliferation and protected against cytokine-induced apoptosis, producing superior beta-cell proliferative effects compared to exenatide. Acute administration of all kisspeptin peptides elevated circulating glucose concentrations, and while KP-14 and KP-10 impaired glucose tolerance, KP-13 did not. Interestingly, KP-14 enhanced glucose-stimulated insulin secretion, with KP-13 and KP-10 being devoid of such actions. All kisspeptin isoforms suppressed food intake, although only KP-13, and especially KP-10 administration, led to an inhibition of feeding. Conclusions: Taken together, these data identify KP-13 as possessing the most favourable overall metabolic actions, based on a combination of beneficial actions on beta-cell health and function together with inhibition of feeding and lack of prominent glucose-elevating actions, suggesting possible therapeutic application for type 2 diabetes.<\/jats:p>","DOI":"10.3390\/metabo16090686","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enzymatic Stability and Comparative Effects of Kisspeptin-14, Kisspeptin-13 and Kisspeptin-10 on Beta-Cell Function, Glucose Homeostasis and Appetite Regulation"],"prefix":"10.3390","volume":"16","author":[{"given":"Julie A.","family":"Spratt","sequence":"first","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Tanday","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dearbhla M.","family":"McGinn","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chidiebere D.","family":"Chukwu","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor A.","family":"Gault","sequence":"additional","affiliation":[{"name":"Centre for Diabetes, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, 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, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dudek, M., Ziarniak, K., and Sliwowska, J.H. 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