title: In vivo treatment with glucagon-like peptide 1 promotes the graft function of fetal islet-like cell clusters in transplanted mice.
abstract: Fetal pancreatic tissue has been suggested as a possible cell source for islet replacement therapy in type 1 diabetes mellitus. This tissue consists of a small amount of beta-cells, but a raft of immature and/or progenitor cells which nonetheless have the potential to proliferate and differentiate into functional insulin-producing cells. Freshly isolated fetal islet-like cell clusters are poorly responsive to glucose challenge, compared with adult islets. Upon exposure to appropriate growth factors and microenvironments, both the expansion and differentiation of fetal islet-like cell clusters can be enhanced. In this study, we investigated the role of exendin-4, a long-acting analogue of glucagon-like peptide 1 in the promotion of functional maturation of transplanted fetal islet-like cell clusters in vivo. Both blood glucose levels and body weights of transplanted diabetic mice treated with exendin-4 improved significantly compared with the transplanted group not subjected to exendin-4 treatment during the 3-month post-transplantation period. In addition, blood glucose levels on formal glucose challenge were also significantly improved by the end of the experiments. In the exendin-4-treated group, there were revascularization and insulin-producing cells as evidenced by positive immunostaining of the Lectins Bandeiraea simplicifolia and insulin, respectively, in the graft bearing kidney. These data indicate that in vivo exendin-4 treatment may enhance the growth and differentiation of fetal mice islet-like cell clusters, thus promoting the functional maturation of the graft after transplantation.
authors.affiliation: Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin.
authors.forename: Po Man
authors.initials: PM
authors.lastname: Suen
authors.forename: Karen
authors.initials: K
authors.lastname: Li
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D042783:Endothelial Cells / Q000187:drug effects; D000077270:Exenatide; D005260:Female; D016332:Fetal Tissue Transplantation; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects; D007515:Islets of Langerhans / Q000166:cytology* / Q000196:embryology / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000494:pharmacology*; D011247:Pregnancy; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide