Beneficial effects of pancreas transplantation: regeneration of pancreatic islets in the spontaneously diabetic Torii rat

AIMS: 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.