title: Comparison of exendin-4 on beta-cell replication in mouse and human islet grafts.
abstract: Exendin-4 can stimulate β-cell replication in mice. Whether it can stimulate β-cell replication in human islet grafts remains unknown. Therefore, we compared the effects of exendin-4 on β-cell replication in mouse and human islet grafts. Islets, isolated from mouse and human donors at different ages, were transplanted into diabetic mice and/or diabetic nude mice that were given bromodeoxyuridine (BrdU) with or without exendin-4. At 4 weeks post-transplantation, islet grafts were removed for insulin and BrdU staining and quantification of insulin(+)/BrdU(+) cells. Although diabetes was reversed in all mice transplanting syngeneic mouse islets from young or old donors, normoglycemia was achieved significantly faster in exendin-4 treated mice. Mouse islet grafts in exendin-4 treated mice had significantly more insulin(+)/BrdU(+) β cells than in untreated mice (P < 0.01). Human islet grafts from ≤22-year-old donors had more insulin(+)/BrdU(+) β cells in exendin-4 treated mice than that in untreated mice (P < 0.01). However, human islet grafts from ≥35-year-old donors contained few insulin(+)/BrdU(+) β cells in exendin-4 treated or untreated mice. Our data demonstrated that the capacity for β-cell replication in mouse and human islet grafts is different with and without exendin-4 treatment and indicated that GLP-1 agonists can stimulate β-cell replication in human islets from young donors.
authors.affiliation: Department of Surgery and Schulze Diabetes Institute, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Guangbin
authors.initials: G
authors.lastname: Weng
authors.forename: Huimin
authors.initials: H
authors.lastname: Yi
authors.forename: Bole
authors.initials: B
authors.lastname: Tian
authors.forename: Timothy D
authors.initials: TD
authors.lastname: O'Brien
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D013045:Species Specificity; D014688:Venoms / Q000378:metabolism*
chemical_list: D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide