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Updated: Sep 25, 2025

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Published on: December 7, 2017
The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion
Mitsuaki Sobajima1, Masato Miyake2, Yoshimasa Hamada2
1Division of Molecular Biology, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan; Department of Molecular Physiology, Diabetes Therapeutics and Research Center, Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan; Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto, Tokushima, 770-8503, Japan; Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, 371-8512, Japan.
Abstract:
Stress-inducible transcription factor ATF4 is essential for survival and identity of β-cell during stress conditions. However, the physiological role of ATF4 in β-cell function is not yet completely understood. To understand the role of ATF4 in glucose-stimulated insulin secretion (GSIS), β-cell-specific Atf4 knockout (βAtf4KO) mice were phenotypically characterized. Insulin secretion and mechanistic analyses were performed using islets from control Atf4f/f and βAtf4KO mice to assess key regulators for triggering and amplifying signals for GSIS. βAtf4KO mice displayed glucose intolerance due to reduced insulin secretion. Moreover, βAtf4KO islets exhibited a decrease in both the insulin content and first-phase insulin secretion. The analysis of βAtf4KO islets showed that ATF4 is required for insulin production and glucose-stimulated ATP and cAMP production. The results demonstrate that ATF4 contributes to the multifaceted regulatory process in GSIS even under stress-free conditions.
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