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

Shimada, Kazunori; Ito, Toshinori; Tanemura, Masahiro; Komoda, Hiroshi; Fumimoto, Yuichi; Kawamoto, Koichi; Nishida, Toshirou; Kaneto, Hideaki; Sawa, Yoshiki

doi:10.1016/j.jss.2007.03.030

« Previous Next »Journal of Surgical Research
Volume 145, Issue 2 , Pages 229-237, April 2008

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

Kazunori Shimada, M.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Toshinori Ito, M.D., Ph.D.
- Department of Complementary and Alternative Medicine, Osaka University Graduate School of Medicine, Osaka, Japan
- To whom correspondence and reprint requests should be addressed at Department of Complementary and Alternative Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Masahiro Tanemura, M.D., Ph.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Hiroshi Komoda, M.D., Ph.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Yuichi Fumimoto, M.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Koichi Kawamoto, M.D., Ph.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Toshirou Nishida, M.D., Ph.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Hideaki Kaneto, M.D., Ph.D.
- Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan
Yoshiki Sawa, M.D., Ph.D.
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

Received 21 December 2006 published online 31 August 2007.

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; 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 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.

Key Words: pancreas transplantation, type 2 diabetes, SDT rats, native pancreas, PDX-1, development, β-cell