Dual-Input Regulation of β-Cell Proliferation by ATF6α and Glucose via E2F1.

ABSTRACT: Finding ways to increase β-cell mass is a key goal of diabetes research. During elevated insulin demand, β-cells turn on endoplasmic reticulum (ER) stress response pathways, and some β-cells enter the cell cycle. ER stress response protein activating transcription factor 6 (ATF6α) induces β-cell proliferation, but only in high glucose. The mechanism by which ATF6α increases proliferation, and the reasons for glucose dependence, remain unknown. Here we show that ATF6α activation in mouse and human islet cells increases expression of E2F1, a key cell cycle driver. E2F1 was required for ATF6α-induced proliferation in high glucose. However, E2F1 remained inactive in normal glucose, possibly because retinoblastoma (Rb), a direct E2F1 inhibitor, was in its dephosphorylated, active state. Indeed,

SUBMITTER: Landa-Galvan HV 

PROVIDER: S-EPMC12622758 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature