Hormonal
Chronic hyperglycemia and oxidative stress induce beta-cell dedifferentiation by altering the balance of PAX4 and ARX gene expression, causing beta-cells to lose insulin-secreting identity and adopt alpha-cell features.
In Type 2 Diabetes, high blood sugar and stress can cause insulin-producing beta-cells to 'forget' their job and turn into glucagon-producing alpha-like cells. This is driven by epigenetic changes to genes like PAX4 and ARX. This loss of identity contributes to worsening blood sugar control, suggesting that therapies aiming to restore beta-cell identity or function could be beneficial.
during T2DM, epigenetic regulation disrupts this balance, inducing the phenomenon of β-cell dedifferentiation, wherein β-cell lose their specialised insulin secreting identity and adopt alpha like cells features. This phenomenon is primarily driven by elevated ARX expression... At the same time, decreased PAX4 expression exacerbates the loss of β-cell identity
Why this rating
Review article citing specific gene targets (PAX4, ARX) and their epigenetic regulation.
Source
Epigenetic regulation in type II diabetes: linking molecular mechanisms to clinical management
Maryam Chaudhry et al. · Journal of Diabetes & Metabolic Disorders · 2026
DOI 10.1007/s40200-025-01831-1
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