Development of β-cells in the native pancreas after pancreas allo-transplantation in the Spontaneously Diabetic Torii rat

Background. We previously demonstrated the development of beta-cells in the native pancreas after syngeneic pancreas transplantation (PTx) in a model of type 2 diabetes, namely the Spontaneously Diabetic Torii (SDT; RT1(a)) rat. In this study, we evaluated the effect of fully allogeneic PTx (allo-PTx) under immunosuppression on the native pancreases in the recipients. Materials and methods. Diabetic 25-week-old SDT rats were divided into two groups: untreated controls and PTx-treated recipients. Dark Agouti (RT1(a)) pancreases were then transplanted into the SDT rats. FK506 was administered daily postoperatively. Each group was examined for 15 weeks. Results. Control SDT rats showed a disappearance of the pancreatic and duodenal homeobox-1 (PDX-1) expression of the pancreases with the development of diabetes. In addition, the islets were gradually replaced by fibrosis, thus resulting in a marked decrease in the beta-cell mass at 40 weeks of age. On the other hand, in PTx recipients, islet-like cell clusters were found in the native pancreases. The beta-cell mass significantly increased in the native pancreases in the recipients at 10 and 15 weeks posttransplantation in comparison to the age-matched controls. Moreover, we observed the re-expression of PDX-1 in the islet-like cell clusters. Interestingly, insulin and glucagon double-positive stained cells in the mesenchyme and insulin single-positive cells in the ductal epithelium were also observed. Conclusions. Our results indicated that the benefits of avoiding glucose toxicity by allo-PTx under immu-nosuppression could therefore induce the PDX-1 expression in the native pancreases, thus potentially resulting in the development of beta-cells in type 2 diabetic recipients. (C) 2008 Elsevier Inc. All rights reserved.