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

Transplant Proc. 2008 Mar;40(2):438-40. doi: 10.1016/j.transproceed.2008.01.019.

Abstract

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.

MeSH terms

  • Animals
  • Blood Glucose / metabolism*
  • Body Weight
  • Diabetes Mellitus, Experimental / surgery*
  • Diabetes Mellitus, Type 2 / surgery*
  • Homeodomain Proteins / genetics
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / physiology*
  • Male
  • Pancreas Transplantation*
  • Rats
  • Rats, Inbred Strains
  • Regeneration
  • Trans-Activators / genetics
  • Transplantation, Homologous
  • Transplantation, Isogeneic

Substances

  • Blood Glucose
  • Homeodomain Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein