Pancreatic Duct Ligation After Almost Complete β-Cell Loss: Exocrine Regeneration but No Evidence of β-Cell Regeneration

There has been great interest in the extent of beta-cell regeneration after pancreatic duct ligation ( PDL) and whether alpha- to beta-cell conversion might account for beta-cell regeneration after near-complete beta-cell loss. To assess these questions, we established a PDL-model in adult male rats after almost complete beta-cell depletion achieved by giving a single high dose of streptozocin (STZ) in the fasted state. Because of the resultant severe diabetes, rats were given islet cell transplants to allow long-term follow-up. Although animals were followed up to 10 months, there was no meaningful beta-cell regeneration, be it through replication, neogenesis, or alpha- to beta-cell conversion. In contrast, the acinar cell compartment underwent massive changes with first severe acinar degeneration upon PDL injury followed by the appearance of pancreatic adipocytes,and finally near-complete reappearance of acini. We conclude that beta-cells and acinar cells, although originating from the same precursors during development, have very distinct regenerative potentials in our PDL model in adult rats.