Extra-insular beta cells associated with ductules are frequent in adult human pancreas

Routine immunohistochemical analysis of human donor pancreata indicated the frequent occurrence of single insulin-immunoreactive cells. In a quantitative analysis of nine organs consecutively recruited from adult donors, 15 percent of all beta cells were found in units with a diameter less than < 20 mu m and without associated glucagon-, somatostatin-, or pancreatic polypeptide cells. These single beta-cell units are located in or along ductules, from which they appear to bud as previously noticed in fetal and neonatal organs. They contain significantly smaller beta cells than endocrine aggregates with a larger diameter. The use of ductal cell markers such as cytokeratin 19, carbonic anhydrase-II and carbohydrate antigen 19.9 identified a close topographical association between ductal cells and budding beta cells; it also indicated that pancreatic lobules are composed of nearly one third ductal cells. The presence of Ki67 proliferation marker-immunoreactive ductal cells (0.05%) and absence of Ki67-immunoreactive budding beta cells is compatible with the view that beta-cell neogenesis depends on ductal cell proliferation and differentiation. The high proportion of budding beta cells in the adult human pancreas suggests the presence of numerous loci with a potential for beta-cell neogenesis.