Under typical circumstances, human β-cells and their cellular precursors are established by young adulthood.

Aim/hypothesis-We measured serum C-peptide in many individuals with chronic type 1 diabetes (T1D) and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of such subjects' persistent anti-beta cell autoimmunity, we speculated that immunosuppression (to weaken the autoimmune attack) and euglycemia accompanying transplant-based treatments for type 1 diabetes (T1D) might promote recovery of T1D subject's native pancreatic beta cell function.Methods-We performed arginine stimulation tests in 3 islet transplant and 4 whole pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. We differentiated insulin secreted from the individual's native pancreatic beta cells and from allografted beta cells based upon each sampling site's C-peptide concentration and kinetics.Results-Selective venous sampling demonstrated that despite long-standing T1D, all 7 beta cell allograft recipients displayed evidence that their native pancreas was a source for secreted C-peptide. Even so, if chronic immunosuppression coupled with near normal glycemia improved native pancreatic C-peptide production, the magnitude of the effect was quite small.Conclusions/interpretation-While some native pancreatic beta cell function persists even years after disease onset in most with T1D, if prolonged euglycemia plus anti-rejection immunosuppressive therapy promotes improved the subjects' native pancreatic insulin production, the effect is small. We may have underestimated pancreatic regenerative capacity by studying only a limited subject number, or by creating conditions (e.g. high circulating insulin concentrations, or immunosuppressive agents toxic to beta cells) that impair beta cell function.