In vivo treatment with glucagon-like peptide 1 promotes the graft function of fetal islet-like cell clusters in transplanted mice.
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.
Suen
Po Man
PM
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin.
Li
Karen
K
Chan
Juliana C N
JC
Leung
Po Sing
PS
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*
D001786:Blood Glucose; D007328:Insulin; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide