Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42455072.
- Also identified by DOI 10.2337/db25-1027.
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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.