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Here, we describe in vitro characterization of the secretory function of pancreatic islets, derived from transgenic pigs expressing the GLP-1M3R cassette under the porcine insulin promoter (InsGLP-1M3R), and their usage to treat insulin-dependent diabetes in an immunodeficient mouse model. Our results show that InsGLP-1M3R islets isolated from neonatal and adult pigs secrete up to 15-fold more insulin in response to glucose stimulation compared to wild-type (WT) islets. They also proved to be more efficient in treating diabetes in a preclinical model as shown by a significantly higher percentage of normoglycemic recipients and higher porcine C-peptide levels up to 9 mo post implantation.<\/jats:p>","DOI":"10.1073\/pnas.2409138121","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T15:05:22Z","timestamp":1730732722000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":12,"title":["Double transgenic neonatal porcine islets as an alternative source for beta cell replacement therapy"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2472-2780","authenticated-orcid":false,"given":"Nizar I.","family":"Mourad","sequence":"first","affiliation":[{"name":"P\u00f4le de chirurgie exp\u00e9rimentale et transplantation, Universit\u00e9 catholique de Louvain, Brussels 1200, Belgium"},{"name":"Pig For Life, Marche-en-Famenne 6900, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0387-8724","authenticated-orcid":false,"given":"Andrea","family":"Perota","sequence":"additional","affiliation":[{"name":"Laboratorio di Tecnologie della Riproduzione, Avantea, Cremona 26100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-8050","authenticated-orcid":false,"given":"Daela","family":"Xhema","sequence":"additional","affiliation":[{"name":"P\u00f4le de chirurgie exp\u00e9rimentale et transplantation, Universit\u00e9 catholique de Louvain, Brussels 1200, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Duchi","sequence":"additional","affiliation":[{"name":"Laboratorio di Tecnologie della Riproduzione, Avantea, Cremona 26100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Lagutina","sequence":"additional","affiliation":[{"name":"Laboratorio di Tecnologie della Riproduzione, Avantea, Cremona 26100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Galli","sequence":"additional","affiliation":[{"name":"Pig For Life, Marche-en-Famenne 6900, Belgium"},{"name":"Laboratorio di Tecnologie della Riproduzione, Avantea, Cremona 26100, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5326-0864","authenticated-orcid":false,"given":"Pierre","family":"Gianello","sequence":"additional","affiliation":[{"name":"P\u00f4le de chirurgie exp\u00e9rimentale et transplantation, Universit\u00e9 catholique de Louvain, Brussels 1200, Belgium"},{"name":"Pig For Life, Marche-en-Famenne 6900, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,11,4]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40472-017-0157-6"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.16876"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0065"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12789"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.898948"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12283"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12747"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708420114"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12659"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12201"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12443"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2022.100370"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1032906"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03913-4"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-007-0844-4"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2009.00548.x"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.3727\/096368916X693798"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.935060"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2007.05.001"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12022"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.2006.00374.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118649"},{"key":"e_1_3_4_23_2","unstructured":"A. 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