{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:53:30Z","timestamp":1790038410028,"version":"4.0.1"},"reference-count":25,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"vor","delay-in-days":68,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"name":"Pays de la Loire Region","award":["Xenothera academic program"],"award-info":[{"award-number":["Xenothera academic program"]}]},{"DOI":"10.13039\/501100001665","name":"National Research Agency \u201cInvestment Into The Future\u201d program","doi-asserted-by":"publisher","award":["ANR-10-IBHU-005"],"award-info":[{"award-number":["ANR-10-IBHU-005"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"National Research Agency \u201cInvestment Into The Future\u201d program","doi-asserted-by":"publisher","award":["0014"],"award-info":[{"award-number":["0014"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004965","name":"Sixth Framework Programme","doi-asserted-by":"publisher","award":["LSHB-CT-2006-037377"],"award-info":[{"award-number":["LSHB-CT-2006-037377"]}],"id":[{"id":"10.13039\/501100004965","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004963","name":"European Seventh Framework Programme \u201cTranslink\u201d research program","doi-asserted-by":"publisher","award":["(grant agreement 603049"],"award-info":[{"award-number":["(grant agreement 603049"]}],"id":[{"id":"10.13039\/501100004963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:p>Xenocell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type 1 diabetes for addressing organ shortage. In humans, however, natural and elicited antibodies specific for pig xenoantigens, \u03b1-(1,3)-galactose (GAL) and N-glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xenoislet rejection. We obtained double-knockout (DKO) pigs lacking GAL and Neu5Gc. Because Neu5Gc\u2212\/\u2212 mice exhibit glycemic dysregulations and pancreatic \u03b2-cell dysfunctions, we evaluated islet function and glucose metabolism regulation in DKO pigs. Isolation of islets from neonate piglets yielded identical islet equivalent quantities to quantities obtained from control wild-type pigs. In contrast to wild-type islets, DKO islets did not induce anti-Neu5Gc antibody when grafted in cytidine monophosphate-N-acetylneuraminic acid hydroxylase KO mice and exhibited in vitro normal insulin secretion stimulated by glucose and theophylline. Adult DKO pancreata showed no histological abnormalities, and immunostaining of insulin and glucagon was similar to that from wild-type pancreata. Blood glucose, insulin, C-peptide, the insulin-to-glucagon ratio, and HOMA-insulin resistance in fasted adult DKO pigs and blood glucose and C-peptide changes after intravenous glucose or insulin administration were similar to wild-type pigs. This first evaluation of glucose homeostasis in DKO pigs for two major xenoantigens paves the way to their use in (pre)clinical studies.<\/jats:p>","DOI":"10.2337\/db16-1060","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T02:20:32Z","timestamp":1484274032000},"page":"987-993","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":34,"title":["Neu5Gc and \u03b11-3 GAL Xenoantigen Knockout Does Not Affect Glycemia Homeostasis and Insulin Secretion in Pigs"],"prefix":"10.2337","volume":"66","author":[{"given":"Apolline","family":"Salama","sequence":"first","affiliation":[{"name":"IECM, Immuno-endocrinology, EA4644 Oniris, University of Nantes, USC1383 INRA, Oniris, Nantes, France"},{"name":"Soci\u00e9t\u00e9 d\u2019Acc\u00e9l\u00e9ration du Transfert de Technologies Ouest Valorisation, Rennes, France"},{"name":"INSERM CRTI UMR 1064, University of Nantes, Nantes, France"},{"name":"Institute of 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