The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion
The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion
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ATF4 在调节葡萄糖刺激的胰岛素分泌中的多方面作用
DOI：
10.1016/j.bbrc.2022.04.038
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发表时间：
2022
影响因子：
3.1
通讯作者：
Oyadomari Seiichi
中科院分区：
文献类型：
--
作者：
Sobajima Mitsuaki;Miyake Masato;Hamada Yoshimasa;Tsugawa Kazue;Oyadomari Miho;Inoue Ryota;Shirakawa Jun;Arima Hiroshi;Oyadomari Seiichi
应激诱导转录因子ATF 4对β细胞在应激条件下的存活和身份是必需的。然而，ATF 4在β细胞功能中的生理作用尚未完全了解。为了了解ATF 4在葡萄糖刺激的胰岛素分泌（GSIS）中的作用，对β细胞特异性Atf 4敲除（β Atf 4KO）小鼠进行了表型表征。使用来自对照Atf 4f/f和β Atf 4KO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信号的关键调节因子。β Atf 4 KO小鼠由于胰岛素分泌减少而表现出葡萄糖耐受不良。此外，β Atf 4 KO胰岛表现出胰岛素含量和第一时相胰岛素分泌减少。对β Atf 4 KO胰岛的分析表明，ATF 4是胰岛素产生和葡萄糖刺激的ATP和cAMP产生所必需的。结果表明，ATF 4有助于GSIS的多方面的监管过程，即使在无压力的条件下。
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.