Development of beta-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.


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 immunosuppression 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.
Shimada
Kazunori
K
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Ito
Toshinori
T
Tanemura
Masahiro
M
Komoda
Hiroshi
H
Fumimoto
Yuichi
Y
Kawamoto
Koichi
K
Nishida
Toshirou
T
Kaneto
Hideaki
H
Sawa
Yoshiki
Y
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002455:Cell Division / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000601:surgery*; D005951:Glucose Tolerance Test; D006085:Graft Survival; D018398:Homeodomain Proteins / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D008297:Male; D016035:Pancreas Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D012038:Regeneration / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism; D014184:Transplantation, Homologous
D001786:Blood Glucose; D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein