Pancreatic duct ligation after almost complete β-cell loss: Exocrine regeneration but no evidence of β-cell regeneration

Abstract

There has been great interest in the extent of β-cell regeneration after pancreatic duct ligation (PDL) and whether α- to β-cell conversion might account for β-cell regeneration after near-complete β-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 β-cell regeneration, be it through replication, neogenesis, or α- to β-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 nearcomplete reappearance of acini. We conclude that β-cells and acinar cells, although originating from the same precursors during development, have very distinct regenerative potentials in our PDL model in adult rats. Copyright © 2013 by The Endocrine Society.