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 I 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 I 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. (c) 2005 Elsevier Ltd. All rights reserved.