The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion

Stress-inducible transcription factor ATF4 is essential for survival and identity of beta -cell during stress conditions. However, the physiological role of ATF4 in beta-cell function is not yet completely understood. To understand the role of ATF4 in glucose-stimulated insulin secretion (GSIS), beta-cell-specific Atf4 knockout (0Atf4KO) mice were phenotypically characterized. Insulin secretion and mechanistic analyses were performed using islets from control Atf4f/f and beta Atf4KO mice to assess key regulators for triggering and amplifying signals for GSIS. beta Atf4KO mice displayed glucose intolerance due to reduced insulin secretion. Moreover, beta Atf4KO islets exhibited a decrease in both the insulin content and first-phase insulin secretion. The analysis of beta Atf4KO 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. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

The stress-inducible transcription factor ATF4 is crucial for the survival and identity of beta-cells during stress conditions. Its role in glucose-stimulated insulin secretion (GSIS) was investigated using beta-cell-specific Atf4 knockout mice. The results showed that ATF4 is essential for insulin production and glucose-stimulated ATP and cAMP production, contributing to the multifaceted regulatory process in GSIS.