Effect of Thioketal Antioxidants on Islet Cell Transplantation

Abstract

AbstractPancreatic islet transplantation is an effective strategy for restoring glucose regulation for highly selected patients with type 1 diabetes. However, an undesirable level of islet cell death is caused by oxidative stress that occurs during islet isolation, culture, and transplantation. The loss of islets throughout the transplantation procedure often necessitates multiple human donors per recipient to achieve insulin independence. Administration of exogenous antioxidants has shown promise in both preserving islet cell viability and functionality post‐transplantation. Herein, thioketal (TK) antioxidant is evaluated using neonatal porcine islets and Beta‐TC‐6 cells exposed to H2O2 for changes in membrane integrity, oxygen consumption rates, and lipid peroxidation. Diabetic BALB/c mice are transplanted with a marginal dose of syngeneic islets, ±48‐h TK pre‐treatment, under the kidney capsule. Graft function is measured by nonfasting blood glucose and glucose tolerance testing. It is found that 200 µM of TK was not cytotoxic, reduced reactive oxygen species‐mediated oxidative islet damage, preserved in vitro islet cell functionality, and facilitated superior murine syngeneic marginal islet mass engraftment. These results demonstrate that the antioxidant attributes of TK reduce the deleterious effects of reactive oxygen species experienced in vitro and enhance marginal islet mass transplant outcomes.