BACKGROUND: Hypoxia in the portal vein may compromise the survival of intraportally transplanted pancreatic islets. We therefore examined the effect of inspired oxygen on the outcome of islet transplantation. METHODS: Blood glucose concentrations, glucose tolerance, and the size and number of surviving islets were measured in diabetic rats housed for 48 hr under hyperoxic (100% O(2)), hypoxic (11% O(2)), or normoxic (21%O(2)) conditions after intraportal transplantation of 350, 500, 700, or 1,000 syngeneic islets. RESULTS: In normoxic diabetic rats, the smallest graft size to consistently restore normoglycemia was 1,000 islets. A graft size of 700 islets was effective in only three of nine animals, whereas 500 islets were ineffective in all eight animals undergoing transplantation. In contrast, in hyperoxically housed rats, graft sizes of 700 or 500 islets restored normoglycemia in eight of nine or five of eight animals, respectively. In those animals that became normoglycemic, the glucose tolerance of the hyperoxically treated rats receiving 700 islets was almost identical to that of normoxically housed animals receiving 1,000 islets. The average size of the islets 6 weeks after transplantation was the same in livers of hyperoxic and control rats. However, the total islet area and number of islets engrafted in hyperoxic rats was significantly increased when compared with livers from normoxic animals receiving the same graft size, so the area in hyperoxic rats receiving 700 islets was not significantly different from normoxic recipients of 1,000 islets. CONCLUSIONS: Hyperoxia posttransplantation increases the number of islets that survive the engraftment process and allows normalization of plasma glucose levels with a smaller number of transplanted islets.
BACKGROUND:Hypoxia in the portal vein may compromise the survival of intraportally transplanted pancreatic islets. We therefore examined the effect of inspired oxygen on the outcome of islet transplantation. METHODS:Blood glucose concentrations, glucose tolerance, and the size and number of surviving islets were measured in diabeticrats housed for 48 hr under hyperoxic (100% O(2)), hypoxic (11% O(2)), or normoxic (21%O(2)) conditions after intraportal transplantation of 350, 500, 700, or 1,000 syngeneic islets. RESULTS: In normoxic diabeticrats, the smallest graft size to consistently restore normoglycemia was 1,000 islets. A graft size of 700 islets was effective in only three of nine animals, whereas 500 islets were ineffective in all eight animals undergoing transplantation. In contrast, in hyperoxically housed rats, graft sizes of 700 or 500 islets restored normoglycemia in eight of nine or five of eight animals, respectively. In those animals that became normoglycemic, the glucose tolerance of the hyperoxically treated rats receiving 700 islets was almost identical to that of normoxically housed animals receiving 1,000 islets. The average size of the islets 6 weeks after transplantation was the same in livers of hyperoxic and control rats. However, the total islet area and number of islets engrafted in hyperoxic rats was significantly increased when compared with livers from normoxic animals receiving the same graft size, so the area in hyperoxic rats receiving 700 islets was not significantly different from normoxic recipients of 1,000 islets. CONCLUSIONS:Hyperoxia posttransplantation increases the number of islets that survive the engraftment process and allows normalization of plasma glucose levels with a smaller number of transplanted islets.
Authors: Barbara Ludwig; Avi Rotem; Janine Schmid; Gordon C Weir; Clark K Colton; Mathias D Brendel; Tova Neufeld; Norman L Block; Karina Yavriyants; Anja Steffen; Stefan Ludwig; Triantafyllos Chavakis; Andreas Reichel; Dimitri Azarov; Baruch Zimermann; Shiri Maimon; Mariya Balyura; Tania Rozenshtein; Noa Shabtay; Pnina Vardi; Konstantin Bloch; Paul de Vos; Andrew V Schally; Stefan R Bornstein; Uriel Barkai Journal: Proc Natl Acad Sci U S A Date: 2012-03-05 Impact factor: 11.205