Transient ER stress cell-autonomously promotes beta cell cycling in mice – published online 15/01/2026

Stephanie Bourgeois, Annelore Van Mulders, Yves Heremans, Gunter Leuckx, Lien Willems, Sophie Coenen, Laure Degroote, Julie Pierreux, Daliya Kancheva, Isabelle Scheyltjens, Kiavash Movahedi, Françoise Carlotti, Eelco de Koning, Xiaoyan Yi, Chiara Vinci, Yue Tong, Miriam Cnop, Harry Heimberg, Nico De Leu, Willem Staels

Regenerating endogenous pancreatic beta cells is a potentially curative yet currently elusive strategy for diabetes therapy. In this issue, Bourgeois et al (https://doi.org/10.1007/s00125-025-06649-3) report that transient endoplasmic reticulum (ER) stress can cell-autonomously stimulate beta cell proliferation in mice. Using two independent transgenic mouse models in which beta cell-specific transgene overexpression induces reversible ER stress, the authors observed the same phenomenon: when transgene expression was halted and ER stress resolved, beta cells showed a marked increase in cell cycle entry, revealing a reproducible, stress-dependent proliferative boost. Complementary in vitro experiments demonstrated that short-term, chemically induced ER stress is sufficient to trigger this proliferative response and that glucose levels modulate the magnitude of the effect. The authors conclude transient ER stress is a regulator of beta cell expansion, opening new avenues for research into diabetes therapies aimed at restoring beta cell mass.

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