A novel resting strategy for improving islet engraftment in the liver

BACKGROUND: Several studies have revealed that posttransplant insulin treatment is beneficial to rest the islet grafts. However, insulin infusion per se is not enough to completely suppress the heavy workload arising caused by postprandial hyperglycemia. Therefore, the present study examined whether short-term fasting combined with insulin treatment could effectively prevent graft exhaustion after intraportal islet transplantation. METHODS: A marginal dose of syngeneic rat islet grafts were transplanted intraportally into the control, insulin-treated, and insulin+rest groups of streptozotocin-induced diabetic rats. The control group fed freely without insulin treatment, and the other groups were continuously treated with an optimal amount of insulin to maintain normoglycemia. In addition, the insulin+rest group fasted and received total parenteral nutrition during the 2 weeks after transplantation. RESULTS: The curative rate was significantly higher in both the insulin and insulin+rest groups than the control group (P<0.0001). The glucose tolerance, residual graft mass, and graft function were significantly ameliorated in the insulin+rest group, but not in the insulin group, compared to the control group (P<0.01, P=0.03, P=0.001). CONCLUSIONS: These data suggest that short-term fasting combined with insulin treatment, especially during the avascular period of the grafts, could therefore be a promising regimen for improving pancreatic islet engraftment in the liver.