Journal Article

Pancreatic injury induces β-cell regeneration in axolotl

Whited, Jessica L, Juarez, Ashley R, Payzin-Dogru, Duygu, Kim, Ryan T, Powell, Connor J, Savage, Aaron M, Dittrich, Anita, Jain, Miten, Lopez, Noah J, Abouelela, Adnan, Akeson, Stuart G, Singer, Hani D, Blair, Steven J

2025

Overview

Diabetes is a condition characterized by a loss of pancreatic β-cell function which results in the dysregulation of insulin homeostasis. Using a partial pancreatectomy model in axolotl, we aimed to observe the pancreatic response to injury. Here we show a comprehensive histological assessment of pancreatic islets in axolotl. Following pancreatic injury, no apparent blastemal structure was observed. We found a significant, organ-wide increase in cellular proliferation post-resection in the pancreas compared to sham-operated controls. This proliferative response was most robust at the site of injury. We found that β-cells actively contributed to the increased rates of proliferation upon injury. β-cell proliferation manifested in increased β-cell mass in injured tissue at two weeks post injury. At four weeks post injury, we found organ-wide proliferation to be extinguished while proliferation at the injury site persisted, corresponding to pancreatic tissue recovery. Similarly, total β-cell mass was comparable to sham after four weeks. Our findings suggest a non-blastema-mediated regeneration process takes place in the pancreas, by which pancreatic resection induces whole-organ β-cell proliferation without the formation of a blastemal structure. This process is analogous to other models of compensatory growth in axolotl, including liver regeneration.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Cell culture / Cell growth / Cell proliferation / Developmental Biology / Diabetes mellitus / Hepatocytes / Homeostasis / Pancreas