Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes.

Authors

Sneha S Varghese, Alessandro Giovanni Hernandez-De La Peña, Liu Wang, Victor Ruiz, Wilma Tixi, Aparamita Pandey, Laura Anchondo, Amy Chiu, Xiwei Wu, Senta K Georgia, Hung-Ping Shih, Zong Wei, Supriyo Bhattacharya, Sangeeta Dhawan

Published in

Diabetes. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Mechanisms underlying the differential susceptibility of pancreatic β- and α-cells to diabetogenic stress remain unclear. We investigated whether replication, repair fidelity, and developmental epigenetic programs determine the vulnerability of postnatal β- and α-cells to DNA damage, a key driver of β-cell failure in diabetes. Replication introduces DNA damage vulnerability in both neonatal β- and α-cells, yet β-cells resolve damage more efficiently. Loss of DNA methyltransferase 3a in pancreatic progenitors selectively heightens β-cell DNA damage vulnerability that persists into adulthood. Moreover, diabetogenic stress preferentially compromises β-cell repair fidelity. These findings reveal how developmental programs shape β-cell resilience and may influence lifelong diabetes risk.

PMID:
42455072
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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