Beneficial effects of pancreas transplantation: regeneration of pancreatic islets in the spontaneously diabetic Torii rat.
OBJECTIVE
Type 2 diabetes is characterized by a combination of insulin resistance and pancreatic beta-cell dysfunction. Although pancreas transplantation (PTx) is mainly performed in patients with type 1 disease, both clinical and experimental data have demonstrated that PTx improves insulin sensitivity in type 2 diabetic recipients. However, it remains unclear whether PTx has the potential to induce islet neogenesis in a recipient's native pancreas.


METHODS
Nondiabetic 10-week-old and diabetic (defined as blood glucose level >250 mg/dL) 25-week-old (average onset age of diabetes) male spontaneously diabetic Torii (SDT; RT1(a)) rats served as donors and recipients, respectively.


RESULTS
In nontreated control SDT rats, beta-cell mass gradually decreased and blood glucose levels progressively increased (>600 mg/dL after 40 weeks of age). In PTx rats, however, the onset of diabetes was significantly delayed (>47.5 +/- 18.2 [graft age] versus 25.2 +/- 3.9 weeks in control rats). On immunohistochemical staining, insulin-secreting islets were observed in the naive pancreata of 40-week-old recipients with PTx (PTx40w), whereas no islets were found in 40-week-old control SDT rats. Moreover, the islets in the native pancreata of PTx40w recipients were located close to ductal structures, and PDX-1 (pancreatic duodenal homeobox-1)-positive cells were more clearly visible. These results indicate the possibility of beta-cell regeneration in the recipient native pancreas by avoiding glucose toxicity under normoglycemic condition achieved by PTx.


CONCLUSIONS
Pancreas transplantation has beneficial effects on impaired islet, inducing regeneration in the spontaneously diabetic Torii rat.
Miao
G
G
Department of Surgery (E1), Osaka University Graduate School of Medicine, Suita, Osaka Japan.
Ito
T
T
Uchikoshi
F
F
Tanemura
M
M
Kawamoto
K
K
Shimada
K
K
Nozawa
M
M
Matsuda
H
H
D000375:Aging / Q000502:physiology; D000818:Animals; D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000601:surgery*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D008297:Male; D016035:Pancreas Transplantation / Q000379:methods / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D012038:Regeneration / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein