Activating Transcription Factor 6α Governs Stress-Adaptive Pancreatic β-Cell Mass Expansion by Coordinating Proliferation and Survival.

Otani, Daisuke; Murakami, Takaaki; Fauzi, Muhammad; Botagarova, Ainur; Sekito, Sho; Tatsuoka, Hisato; Tokumoto, Shinsuke; Usui, Ryota et al. · Diabetes · 2026

basic_science · Level V

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Abstract

The role of activating transcription factor 6α (ATF6α) in the stress-adaptive regulation of pancreatic β-cell mass (BCM) in vivo remains incompletely defined. We investigated the role of ATF6α in the regulation of BCM, β-cell proliferation, and survival under sustained stress using in vivo and in vitro models. Loss of ATF6α consistently impaired BCM expansion through reduced β-cell proliferation and increased apoptosis across models. Our findings establish ATF6α as an important regulator of stress-adaptive BCM expansion through coordinating β-cell survival and proliferation under sustained stress.