{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:42:06Z","timestamp":1772160126362,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","award":["Early career research award"],"award-info":[{"award-number":["Early career research award"]}],"id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001632","name":"Ulster University","doi-asserted-by":"publisher","award":["Vice\u2010Chancellor PhD research scholarship"],"award-info":[{"award-number":["Vice\u2010Chancellor PhD research scholarship"]}],"id":[{"id":"10.13039\/501100001632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To assess the beneficial metabolic effects of the nonapeptide hormone, arginine vasopressin (AVP), on metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We exchanged amino acids at position 3 and 8 of AVP, namely phenylalanine and arginine, with those of oxytocin, to generate novel analogues with altered receptor selectivity. Secondary modification by N\u2010terminal acetylation was used to impart stability to circulating endopeptidases. Analogues were screened for degradation, bioactivity in rodent\/human clonal beta cells and primary murine islets, together with evaluation of receptor activation profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Analogue Ac3IV, which lacked effects at the V2 receptors responsible for modulation of fluid balance, was selected as the lead compound for assessment of antidiabetic efficacy in high\u2010fat\u2010fed mice. Twice\u2010daily administration of Ac3IV, or the gold standard control exendin\u20104, for 22\u2009days, reduced energy intake as well as body weight and fat content. Both interventions decreased circulating glucose levels, enhanced insulin sensitivity, and substantially improved glucose tolerance and related insulin secretion in response to an intraperitoneal or oral glucose challenge. The peptides decreased total\u2010 and increased HDL\u2010cholesterol, but only Ac3IV decreased LDL\u2010cholesterol, triglyceride and non\u2010fasting glucagon concentrations. Elevations of islet and beta\u2010cell areas were partially reversed, accompanied by suppressed islet cell proliferation, decreased beta\u2010cell apoptosis and, in the case of exendin\u20104, also decreased alpha\u2010cell apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>AVP\u2010based therapies that exclusively target V1a and V1b receptors may have significant therapeutic potential for the treatment of obesity and related diabetes, and merit further clinical exploration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14462","type":"journal-article","created":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T05:27:59Z","timestamp":1623216479000},"page":"2215-2225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Weight\u2010reducing, lipid\u2010lowering and antidiabetic activities of a novel arginine vasopressin analogue acting at the V1a and V1b receptors in high\u2010fat\u2010fed mice"],"prefix":"10.1111","volume":"23","author":[{"given":"Shruti","family":"Mohan","sequence":"first","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes University of Ulster  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter R.","family":"Flatt","sequence":"additional","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes University of Ulster  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4855-964X","authenticated-orcid":false,"given":"Nigel","family":"Irwin","sequence":"additional","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes University of Ulster  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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