Evidence of a negative feedback system regulating the total beta-cell volume in nondiabetic rats that received pancreas transplants

Background. The aim of the present study was to investigate the long-term r egulation of pancreatic p-cell volume after pancreas transplantation into a dult rats. Methods. A syngeneic pancreaticoduodenal transplantation was made in normog lycemic Wistar-Furth rats. By this means, the recipients doubled their panc reatic islet volume. Nine months after transplantation, the total beta-cell volume was measured in serial pancreatic sections immunostained for insuli n from both the native and transplanted pancreata, and in the native pancre as of age-matched Wistar-Furth rats that did not receive transplants. Results. No changes in the volume of individual beta-cells were seen. A 50% decrease in total beta-cell volume was observed in both the native and tra nsplanted pancreas when compared with that of age-matched controls. However , the combined beta-cell volumes of the native and transplanted pancreas in the rats that received transplants were similar to those of the native pan creas in control animals. No signs of increased apoptosis in any of the gla nds could be seen during the first postoperative week, or after 9 months. Conclusions. These-findings provide evidence of a negative feedback system, which regulates the total beta-cell volume to the levels seen in age-match ed rats that did not receive transplants. The underlying mechanisms for the decreased beta-cell volume are unknown, but may involve a diminished repli catory rate of the beta-cells.