{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:36:33Z","timestamp":1773794193741,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":289,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3N0982"],"award-info":[{"award-number":["CMRPG3N0982"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3N0981"],"award-info":[{"award-number":["CMRPG3N0981"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3M1241"],"award-info":[{"award-number":["CMRPG3M1241"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3J1552"],"award-info":[{"award-number":["CMRPG3J1552"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3J1551"],"award-info":[{"award-number":["CMRPG3J1551"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3G1961"],"award-info":[{"award-number":["CMRPG3G1961"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 105-2314-B-182A-083"],"award-info":[{"award-number":["MOST 105-2314-B-182A-083"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    Porcine neonatal pancreatic cell clusters (NPCCs) are a promising and abundant source for islet transplantation owing to their ability to secrete insulin and proliferative potential. However, a significant limitation is the delayed normalization of blood glucose following transplantation, largely attributed to incomplete\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cell differentiation. Exendin\u20104, a glucagon\u2010like peptide\u20101 receptor agonist, has been shown to enhance\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cell differentiation, proliferation, and function in various models. This study was aimed at investigating whether posttransplant treatment with exendin\u20104 could accelerate NPCC differentiation and improve long\u2010term glycemic outcomes in diabetic nude mice. NPCCs were isolated from 1\u2010 to 3\u2010day\u2010old piglets and transplanted under the kidney capsule of streptozotocin\u2010induced diabetic nude mice. Recipients received subcutaneous injection of either exendin\u20104 (3\u2009\n                    <jats:italic>\u03bc<\/jats:italic>\n                    g\/kg) or saline (as control) twice daily. Graft differentiation was assessed at Days 6, 9, and 16 via immunostaining for insulin, glucagon, PDX1, and SOX9. Blood glucose levels, body weight, and graft histology were monitored over time. Exendin\u20104 treatment significantly increased the proportion of mature insulin\n                    <jats:sup>+<\/jats:sup>\n                    cells at Day 9 (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.05) and both PDX1\n                    <jats:sup>+<\/jats:sup>\n                    \/insulin\n                    <jats:sup>\u2212<\/jats:sup>\n                    and SOX9\n                    <jats:sup>+<\/jats:sup>\n                    progenitor cells at Day 6 (\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.01). By Week 10, hyperglycemia persisted in both groups; however, exendin\u20104\u2010treated recipients exhibited a significant reduction in blood glucose from Week 6 onward. At this time point, grafts from hyperglycemic mice displayed both insulin\n                    <jats:sup>\u2212<\/jats:sup>\n                    \/PDX1\n                    <jats:sup>+<\/jats:sup>\n                    (progenitor cells) and insulin\n                    <jats:sup>+<\/jats:sup>\n                    \/PDX1\n                    <jats:sup>+<\/jats:sup>\n                    (mature)\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cells, indicating ongoing differentiation. Among mice maintained beyond 10 weeks, euglycemia was achieved between Days 119 and 308, with grafts exhibiting mature insulin\n                    <jats:sup>+<\/jats:sup>\n                    \/PDX1\n                    <jats:sup>+<\/jats:sup>\n                    cells\u2014evidence of morphological and functional maturation. Our results indicate that exendin\u20104 transiently enhances NPCC differentiation and expands the progenitor population in early posttransplantation phases. Furthermore, it contributes to improved graft performance and glycemic control, likely through its well\u2010established metabolic effects.\n                  <\/jats:p>","DOI":"10.1155\/jdr\/5847576","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:49:58Z","timestamp":1760762998000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Exendin\u20104 on the Differentiation and Function of Transplanted Porcine Neonatal Pancreatic Cell Clusters in Diabetic Nude Mice"],"prefix":"10.1155","volume":"2025","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-6059","authenticated-orcid":false,"given":"Jyuhn-Huarng","family":"Juang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Wei","family":"Kao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Ling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0481-4215","authenticated-orcid":false,"given":"Wan-Chun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200007273430401"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.7.2060"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061267"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118649"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.5.8162"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200104270-00024"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2009.03.057"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.4.1032"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1375"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.8.8973"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209423200"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220897"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.12.2270"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00007.2004"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2003.11.006"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-006-0251-2"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368908786092766"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1922-0"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2005.08.005"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020137"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-26404-6"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(00)02239-9"}],"container-title":["Journal of Diabetes Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jdr\/5847576","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/jdr\/5847576","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/jdr\/5847576","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T20:48:16Z","timestamp":1773780496000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/jdr\/5847576"}},"subtitle":[],"editor":[{"given":"Naoaki","family":"Sakata","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1155\/jdr\/5847576"],"URL":"https:\/\/doi.org\/10.1155\/jdr\/5847576","archive":["Portico"],"relation":{},"ISSN":["2314-6745","2314-6753"],"issn-type":[{"value":"2314-6745","type":"print"},{"value":"2314-6753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2025-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"5847576"}}