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.


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.
Shimada
K
K
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Ito
T
T
Miao
G
G
Tanemura
M
M
Komoda
H
H
Fumimoto
Y
Y
Kawamoto
K
K
Nishida
T
T
Kaneto
H
H
Sawa
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000601:surgery*; D018398:Homeodomain Proteins / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D016035:Pancreas Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D012038:Regeneration; D015534:Trans-Activators / Q000235:genetics; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D001786:Blood Glucose; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein