title: Activin A, exendin-4, and glucose stimulate differentiation of human pancreatic ductal cells.
abstract: Islet transplantation is one treatment option for diabetes mellitus. However, novel sources of pancreatic islets or insulin-producing cells are required because the amount of donor tissue available is severely limited. Pancreatic ductal cells are an alternative source of β-cells because they have the potential to differentiate into insulin-producing cells. We investigated whether treatment of human pancreatic ductal cells with activin A (ActA) and exendin-4 (EX-4) stimulated transdifferentiation of the cells, both in vitro and in vivo. We treated human pancreatic ductal cells with ActA and EX-4 in high-glucose media to induce differentiation into insulin-producing cells and transplanted the cells into streptozotocin-induced diabetic nude mice. Co-treatment of mice with ActA and EX-4 promoted cell proliferation, induced expression of pancreatic β-cell-specific markers, and caused glucose-induced insulin secretion compared with the ActA or EX-4 mono-treatment groups respectively. When pancreatic ductal cells treated with ActA and EX-4 in high-glucose media were transplanted into diabetic nude mice, their blood glucose levels normalized and insulin was detected in the graft. These findings suggest that pancreatic ductal cells have a potential to replace pancreatic islets for the treatment of diabetes mellitus when the ductal cells are co-treated with ActA, EX-4, and glucose to promote their differentiation into functional insulin-producing cells.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute, Samsung Medical Center, #50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Republic of Korea Korea.
authors.forename: Hyo-Sup
authors.initials: HS
authors.lastname: Kim
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Hong
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Oh
authors.forename: Jae-Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Myung-Shik
authors.initials: MS
authors.lastname: Lee
authors.forename: Moon-Kyu
authors.initials: MK
authors.lastname: Lee
mesh_terms: D028341:Activins / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D000077270:Exenatide; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D010183:Pancreatic Ducts / Q000166:cytology* / Q000187:drug effects* / Q000637:transplantation; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D007328:Insulin; D010455:Peptides; D014688:Venoms; C422405:activin A; D028341:Activins; D000077270:Exenatide; D005947:Glucose