Development of β-Cells in the Native Pancreas After Pancreas Allo-Transplantation in the Spontaneously Diabetic Torii Rat

• Published in: The Journal of surgical research Vol. 145; no. 2; pp. 229 - 237
• Main Authors: Shimada, Kazunori, M.D, Ito, Toshinori, M.D., Ph.D, Tanemura, Masahiro, M.D., Ph.D, Komoda, Hiroshi, M.D., Ph.D, Fumimoto, Yuichi, M.D, Kawamoto, Koichi, M.D., Ph.D, Nishida, Toshirou, M.D., Ph.D, Kaneto, Hideaki, M.D., Ph.D, Sawa, Yoshiki, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Glucose; Body Weight; Cell Division - physiology; development; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - surgery; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose Tolerance Test; Graft Survival; Homeodomain Proteins - metabolism; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - physiology; Male; Medical sciences; native pancreas; Pancreas Transplantation; PDX-1; Rats; Rats, Inbred Strains; Rats, Mutant Strains; Regeneration - physiology; SDT rats; Surgery; Trans-Activators - metabolism; Transplantation, Homologous; type 2 diabetes; β-cell; development; type 2 diabetes; SDT rats; native pancreas; pancreas transplantation; β-cell; PDX-1; Endocrinopathy; Type 2 diabetes; Rat; Rodentia; Langerhans islet; Metabolic diseases; Homotransplantation; Medicine; Vertebrata; Mammalia; Treatment; Animal; Surgery; Development; Graft; β Cell; Pancreas; Transcription factor PDX-1
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2007.03.030

Background We previously demonstrated the development of β-cells in the native pancreas after syngeneic pancreas transplantation (PTx) in a model of type 2 diabetes, namely the Spontaneously Diabetic Torii (SDT; RT1a ) 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 (RT1a ) 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 β-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 β-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 immunosuppression could therefore induce the PDX-1 expression in the native pancreases, thus potentially resulting in the development of β-cells in type 2 diabetic recipients.