{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:39:42Z","timestamp":1777509582441,"version":"3.51.4"},"reference-count":37,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2008,6,1]],"date-time":"2008-06-01T00:00:00Z","timestamp":1212278400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:p>Pancreatic islet transplantation as a treatment for type 1 diabetes is limited by human donor tissue availability. We investigated whether the \u03b2-cell mass in human isolated islets could be expanded by treatments with glucagon-like peptide-1 (GLP-1) and gastrin, peptides reported to stimulate \u03b2-cell growth in mice and rats with deficits in \u03b2-cell mass. Human islets with low endocrine cell purity (7% \u03b2-cells, 4% \u03b1-cells) and abundant exocrine cells (29% duct cells and 25% acinar cells) were implanted under the renal capsule of nonobese diabetic-severe combined immune deficiency (NOD-scid) mice made diabetic with streptozotocin. The mice were treated with GLP-1 and gastrin, separately and together, daily for 5 weeks. Blood glucose was significantly reduced only in mice implanted with human pancreatic cells and treated with GLP-1 plus gastrin. Correction of hyperglycemia was accompanied by increased insulin content in the human pancreatic cell grafts as well as by increased plasma levels of human C-peptide in the mice. Immunocytochemical examination revealed a fourfold increase in insulin-positive cells in the human pancreatic cell grafts in GLP-1 plus gastrin-treated mice, and most of this increase was accounted for by the appearance of cytokeratin 19-positive pancreatic duct cells expressing insulin. We conclude that combination therapy with GLP-1 and gastrin expands the \u03b2-cell mass in human islets implanted in immunodeficient diabetic mice, largely from pancreatic duct cells associated with the islets, and this is sufficient to ameliorate hyperglycemia in the mice.<\/jats:p>","DOI":"10.3727\/096368908786092775","type":"journal-article","created":{"date-parts":[[2008,10,15]],"date-time":"2008-10-15T22:12:10Z","timestamp":1224108730000},"page":"631-640","source":"Crossref","is-referenced-by-count":63,"title":["Combination Therapy with Glucagon-Like Peptide-1 and Gastrin Induces \u03b2-Cell Neogenesis from Pancreatic Duct Cells in Human Islets Transplanted in Immunodeficient Diabetic Mice"],"prefix":"10.1177","volume":"17","author":[{"given":"Wilma L.","family":"Suarez-Pinzon","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan R. T.","family":"Lakey","sequence":"additional","affiliation":[{"name":"Clinical Islet Transplantation Group Inc., Edmonton, Alberta T6G 2C8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2008,6,1]]},"reference":[{"key":"bibr1-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.14.7999"},{"key":"bibr2-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1115"},{"key":"bibr3-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050960"},{"key":"bibr4-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00025.2004"},{"key":"bibr5-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0015"},{"key":"bibr6-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.124"},{"key":"bibr7-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"bibr8-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.7.1571"},{"key":"bibr9-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0306"},{"key":"bibr10-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1935-8"},{"key":"bibr11-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.8.2007"},{"key":"bibr12-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.10.1671"},{"key":"bibr13-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1038\/nm1367"},{"key":"bibr14-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.4.5882"},{"key":"bibr15-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1620167"},{"key":"bibr16-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1177\/096368979900800309"},{"key":"bibr17-096368908786092775","doi-asserted-by":"publisher","DOI":"10.3109\/00365528109181994"},{"key":"bibr18-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0832"},{"key":"bibr19-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1038\/73128"},{"key":"bibr20-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diab.37.4.413"},{"key":"bibr21-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.29.03.06.dc05-1538"},{"key":"bibr22-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1287-1"},{"key":"bibr23-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051468"},{"key":"bibr24-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.3.686"},{"key":"bibr25-096368908786092775","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.7.2148"},{"key":"bibr26-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061267"},{"key":"bibr27-096368908786092775","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70292-1"},{"key":"bibr28-096368908786092775","first-page":"3107","volume":"53","author":"Street C. 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