Metallothionein overexpression prolongs grafts survival in the early phase of pancreatic islet transplantation.
Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Epstein, Paul N.
Islands of Langerhans; Diabetes--Surgery
Pancreatic islet transplantation is a very promising treatment for type I diabetes. Many clinical trials have failed due to early islet loss and immune rejection. Reactive oxygen species (ROS) have been demonstrated to be involved in graft damage during transplantation. Metallothionein (MT) is an inducible antioxidant protein. Prior studies in our laboratory have shown that overexpression of MT in beta-cells reduces DNA damage and diabetes induced by streptozotocin (STZ), which damages beta cells by generating ROS. Therefore in this study we examined whether overexpression of MT in beta cells is beneficial to pancreatic islet transplantation. Isolated MT transgenic and normal FVB islets were transplanted under the kidney capsule of Balb/c mice that were treated with STZ to induce severe diabetes. We found that diabetic mice transplanted with MT islets maintained near normal glucose levels for 16.2 [plus or minus] 2.52 days while those animals transplanted with control islets maintained normal glucose values for only 8.36 [plus or minus] 1.67 days (p < 0.01). To determine whether the early benefit of MT was due to protection from early islet loss or from immune rejection, islets were transplanted into same strain mice, thereby free of immune rejection.
Li, Xiaoyan, "Metallothionein overexpression prolongs grafts survival in the early phase of pancreatic islet transplantation." (2002). Electronic Theses and Dissertations. Paper 829.