title: 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 near-complete 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.
authors.affiliation: Section on Islet Cell and Regenerative Biology, Research Division, Joslin Diabetes Center, Department of Medicine, Harvard Medical School, One Joslin Place, Boston, Massachusetts 02215. gordon.weir@joslin.harvard.edu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cavelti-Weder
authors.forename: Maria
authors.initials: M
authors.lastname: Shtessel
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Reuss
authors.forename: Agnes
authors.initials: A
authors.lastname: Jermendy
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Yamada
authors.forename: Francisco
authors.initials: F
authors.lastname: Caballero
authors.forename: Susan
authors.initials: S
authors.lastname: Bonner-Weir
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D019394:Ki-67 Antigen / Q000378:metabolism; D008026:Ligation; D008297:Male; D010183:Pancreatic Ducts / Q000601:surgery*; D010191:Pancreatic Polypeptide / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration / Q000502:physiology*
chemical_list: D007328:Insulin; D019394:Ki-67 Antigen; D010191:Pancreatic Polypeptide; D005934:Glucagon
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