MNX1 prevents somatostatin expression in human beta cells by repressing PERCC1 – Published online 08/12/2025

Farah Kobaisi, Alexis Fouque, Philippe Ravassard, Olivier Albagli‑Curiel, Raphael Scharfmann

Blood glucose regulation is managed by specialised pancreatic endocrine cells, mainly beta cells. As the sole producers of insulin, their functionality depends on the strict maintenance of their cellular identity. In diabetes, a loss of this identity results in dysfunction, where beta cells revert to an immature state and fail to secrete insulin. In this issue, Kobaisi et al (https://doi.org/10.1007/s00125-025-06620-2) identify the transcription factor MNX1 (motor neuron and pancreas homeobox 1) as a master regulator that prevents this identity crisis. MNX1 works by actively silencing a secondary gene called PERCC1. Without this inhibition, PERCC1 acts as a central hub that triggers the activation of the HHEX and SST genes, forcing beta cells to adopt the characteristics of somatostatin-producing delta cells. The authors conclude that  the MNX1–PERCC1 axis provides a new target for therapies designed to conserve beta cell identity and restore natural insulin production.

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