{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:42:20Z","timestamp":1772160140332,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"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","id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001632","name":"Ulster University","doi-asserted-by":"publisher","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":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      The aim of the present study was to assess the long\u2010term therapeutic efficacy of a recently discovered 28 amino acid peptide, \u0394\u2010theraphotoxin\u2010Ac1 (\u0394\u2010TRTX\u2010Ac1), originally isolated from venom of the\n                      <jats:italic>Aphonopelma chalcodes<\/jats:italic>\n                      tarantula. \u0394\u2010TRTX\u2010Ac has previously been shown to improve pancreatic beta\u2010cell function and suppress appetite.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\u0394\u2010TRTX\u2010Ac1 was administered twice daily in high\u2010fat fed (HFF) mice with streptozotocin (STZ)\u2010induced insulin deficiency, namely HFF\/STZ mice, for 28\u2009days both alone and in combination with the venom\u2010derived glucagon\u2010like peptide\u20101 (GLP\u20101) mimetic, exenatide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Initial pharmacokinetic profiling of \u0394TRTX\u2010Ac1 revealed a plasma half\u2010life of 2\u2009h in mice, with \u0394TRTX\u2010Ac1 also evidenced in the pancreas 12\u2009h post\u2010injection. Accordingly, HFF\u2010STZ mice received twice\u2010daily injections of \u0394\u2010TRTX\u2010Ac1, exenatide or a combination of both peptides for 28\u2009days. As anticipated, HFF\/STZ mice presented with hyperglycaemia, impaired glucose tolerance, decreased plasma and pancreatic insulin and disturbed pancreatic islet morphology. Administration of \u0394TRTX\u2010Ac1 reduced body weight, improved glucose tolerance and augmented pancreatic insulin content while decreasing glucagon content. Exenatide had similar benefits on body weight and pancreatic hormone content while also reducing circulating glucose. \u0394TRTX\u2010Ac1 decreased energy expenditure on day 28 whereas exenatide had no impact. All treatment regimens restored pancreatic islet and beta\u2010cell area towards lean control levels, which was linked to significantly elevated beta\u2010cell proliferation rates. In terms of benefits of combined \u0394TRTX\u2010Ac1 and exenatide treatment over individual agents, there was augmentation of glucose tolerance and ambulatory activity with combination therapy, and these mice presented with increased pancreatic glucagon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data highlight the therapeutic promise of \u0394TRTX\u2010Ac1 for diabetes, with suggestion that benefits could be enhanced through combined administration with exenatide.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15319","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T01:02:42Z","timestamp":1697072562000},"page":"329-338","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sustained metabolic benefits of\n                    <scp>\u0394TRTX\u2010Ac1<\/scp>\n                    , a tarantula venom\u2010derived peptide, when administered together with exenatide in high\u2010fat fed mice"],"prefix":"10.1111","volume":"26","author":[{"given":"Aimee","family":"Coulter\u2010Parkhill","sequence":"first","affiliation":[{"name":"Diabetes Research Centre Ulster University  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Tanday","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre Ulster University  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Cobice","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre Ulster University  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre Ulster University  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"McClean","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre Ulster University  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-1013","authenticated-orcid":false,"given":"Victor A.","family":"Gault","sequence":"additional","affiliation":[{"name":"Diabetes Research Centre Ulster University  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":"Diabetes Research Centre Ulster University  Coleraine UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2019.107843"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2021.503437"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30381-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.09.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42531-8"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15485"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2023.2192865"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12824"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115544"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80306-2"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.04.06.db05-0788"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175855"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2005.05.004"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S275898"},{"key":"e_1_2_9_16_1","first-page":"265","article-title":"Comparison of sub\u2010chronic metabolic effects of stable forms of naturally occurring GIP (1\u201030) and GIP (1\u201042) in high\u2010fat fed mice","volume":"208","author":"Gault VA","year":"2011","journal-title":"J Endocrinol"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-22-0106"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13908"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00252768"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.674704"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2016.07.020"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.14699"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2146\/ajhp050459"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006070778"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15647"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.10.1.62"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14794"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15083"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21107"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2006.01196.x"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.01.072"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12390"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-021-00582-z"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1728"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.2007.S443"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307612200"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/8083417","article-title":"The effects of exenatide once weekly (EXQW) and exenatide twice a day (EXBID) on beta\u2010cell function in type 2 diabetes: a systematic review and network meta\u2010analysis","volume":"2019","author":"Wang J","year":"2019","journal-title":"J Diabetes Res"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-19-0451"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.10.032"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01452.x"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/11795514211006071"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2017.1377613"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.15319","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T02:30:38Z","timestamp":1761877838000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.15319"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,11]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/dom.15319"],"URL":"https:\/\/doi.org\/10.1111\/dom.15319","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.15319\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v2\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v3\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.15319\/v3\/response1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,11]]},"assertion":[{"value":"2023-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}