Division 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.
Division 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.
Biochem Biophys Res Commun. 2022 Jun 30;611:165-171. doi: 10.1016/j.bbrc.2022.04.038. Epub 2022 Apr 16.
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.
应激诱导转录因子 ATF4 是 β 细胞在应激条件下存活和维持身份的必需因子。然而，ATF4 在 β 细胞功能中的生理作用尚不完全清楚。为了了解 ATF4 在葡萄糖刺激胰岛素分泌（GSIS）中的作用，对β细胞特异性 Atf4 敲除（βAtf4KO）小鼠进行了表型特征分析。使用来自对照 Atf4f/f 和 βAtf4KO 小鼠的胰岛进行胰岛素分泌和机制分析，以评估触发和放大 GSIS 信号的关键调节剂。βAtf4KO 小鼠由于胰岛素分泌减少而表现出葡萄糖不耐受。此外，βAtf4KO 胰岛的胰岛素含量和第一时相胰岛素分泌均减少。βAtf4KO 胰岛的分析表明，ATF4 是胰岛素产生以及葡萄糖刺激的 ATP 和 cAMP 产生所必需的。结果表明，即使在无应激条件下，ATF4 也有助于 GSIS 的多方面调节过程。
