title: Effect of glucagon-like peptide-1 gene expression on graft function in mouse islet transplantation.
abstract: This study investigated the effect of local glucagon-like peptide-1 (GLP-1) production within mouse islets on cytoprotection in vitro and in vivo by gene transfer of GLP-1. Transduction of recombinant adenovirus vector expressing GLP-1 (rAd-GLP-1) induced a significant increase in bioactive GLP-1 in the mouse islet culture, whereas transduction with adenovirus vector expressing β-galactosidase (rAd-LacZ), as a control, had no effect on GLP-1 secretion. Islets transduced with rAd-GLP-1 were protected from H(2) O(2) -induced cell damage in vitro. In addition, glucose-stimulated insulin secretion was significantly increased in rAd-GLP-1-transduced islets. When transplanted under the kidney capsule of diabetic syngeneic mice, islet grafts retrieved 4 or 7 days after transplantation revealed that the rAd-GLP-1-transduced group had significantly more Ki67-positive cells as compared with the rAd-LacZ-transduced group. Regarding blood glucose control, diabetic mice transplanted with a marginal mass of rAd-GLP-1-transduced islets became normoglycemic more rapidly and 78% of the recipients were normoglycemic at 35 days post-transplant, whereas only 48% of the mice transplanted with rAd-LacZ-transduced islets were normoglycemic (P < 0.05). In conclusion, delivery of the GLP-1 gene to islets enhanced islet cell survival during the early post-transplant period, and preserved islet mass and functions over time in the transplants.
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Chae
authors.forename: Jun Goo
authors.initials: JG
authors.lastname: Kang
authors.forename: Chul Sik
authors.initials: CS
authors.lastname: Kim
authors.forename: Seong Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
authors.forename: Dongchul
authors.initials: D
authors.lastname: Kang
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Ihm
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D015870:Gene Expression; D015316:Genetic Therapy; D052216:Glucagon-Like Peptide 1 / Q000235:genetics*; D006085:Graft Survival; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D052216:Glucagon-Like Peptide 1