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Induced pluripotent stem cells (iPSCs) provide an alternative source for generating insulin-producing cells; however, whether the somatic cell origin of human iPSCs influences pancreatic endocrine differentiation remains incompletely defined. In this study, we generated iPSCs from human pancreatic duct cells (HD-iPSCs) and compared their differentiation propensity and functional characteristics with human fibroblast-derived iPSCs (HF-iPSCs) under identical differentiation conditions. HD-iPSC-derived cells showed higher expression of pancreatic endocrine and \u03b2-cell-associated markers, including insulin, PDX1, and FOXA2, compared with HF-iPSC-derived cells. Flow cytometric analysis further confirmed a higher proportion of insulin-positive cells in differentiated HD-iPSC-derived cells. Functionally, HD-iPSC-derived cells exhibited greater glucose-stimulated C-peptide secretion than HF-iPSC-derived cells, although their secretory capacity remained lower than that of native human islets. Following transplantation into streptozotocin-induced diabetic mice, HD-iPSC-derived cells reduced blood glucose levels more effectively than HF-iPSC-derived cells, and insulin-positive grafts were detected in vivo. These findings suggest that human pancreatic duct cell-derived iPSCs have enhanced pancreatic endocrine differentiation potential compared with fibroblast-derived iPSCs. Although further maturation and optimization are required, pancreatic duct cells may represent a favorable somatic cell source for generating iPSC-derived insulin-producing cells for diabetes cell therapy.<\/jats:p>","DOI":"10.1177\/09636897261469970","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:55:41Z","timestamp":1784375741000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Human pancreatic duct cell-derived iPSCs show enhanced differentiation into insulin-producing cells"],"prefix":"10.1177","volume":"35","author":[{"given":"Sung-Bin","family":"Lim","sequence":"first","affiliation":[{"name":"Sungkyunkwan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8728-7184","authenticated-orcid":false,"given":"Moon-Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Eulji University School of 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