Regeneration of beta cells in the native pancreata after syngeneic and allogeneic pancreas transplantations in spontaneously type 2 diabetic Torii rats.

Background: We previously demonstrated that syngeneic pancreas transplantation has a potential to reverse diabetes even in a rat model of type 2 diabetes mellitus, namely Spontaneously Diabetic Torii (SDT; RT1a). The onset of diabetes was significantly delayed in the pancreas transplant recipients. We speculated that perfect diabetic control achieved by pancreas transplantation showed a beneficial effect on the native pancreata & recipients.

Materials And Methods: Twenty-five-week-old diabetic SDT rats were divided into 3 groups: untreated controls and syngeneic and allogeneic transplant recipients. We transplanted pancreaticoduodenal grafts from nondiabetic 10-week-old SDT rats and from 10-week-old allogeneic Dark Agouti (DA; RT1a) rats using daily administration of FK506.

Results: Untreated SDT rats showed disappearance of pancreatic and duodenal homeobox-1 (PDX-1) expression in the pancreas and a marked decrease in beta-cell mass. Among syngeneic and allogeneic pancreas transplant recipients, islet-like cell clusters were found in the native pancreata. The beta-cell mass at 40 weeks of age was significantly increased in the native pancreata of recipients compared with age-matched controls. Interestingly, we observed the reexpression of PDX-1 in the nuclei of islet-like cell clusters.

Conclusions: Our results indicated the benefits of avoiding glucose toxicity by pancreas transplantation which induced PDX-1 expression in the native pancreata of type 2 diabetic recipients, resulting in regeneration of beta cells in the native pancreata.