ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress

Suguru Yamaguchi, Hisamitsu Ishihara, Takahiro Yamada, Akira Tamura, Masahiro Usui, Ryu Tominaga, Yuichiro Munakata, Chihiro Satake, Hideki Katagiri, Fumi Tashiro, Hiroyuki Aburatani, Kyoko Tsukiyama-Kohara, Jun ichi Miyazaki, Nahum Sonenberg, Yoshitomo Oka

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Endoplasmic reticulum (ER) stress-mediated apoptosis may play a crucial role in loss of pancreatic β cell mass, contributing to the development of diabetes. Here we show that induction of 4E-BP1, the suppressor of the mRNA 5′ cap-binding protein eukaryotic initiation factor 4E (eIF4E), is involved in β cell survival under ER stress. 4E-BP1 expression was increased in islets under ER stress in several mouse models of diabetes. The Eif4ebp1 gene encoding 4E-BP1 was revealed to be a direct target of the transcription factor ATF4. Deletion of the Eif4ebp1 gene increased susceptibility to ER stress-mediated apoptosis in MIN6 β cells and mouse islets, which was accompanied by deregulated translational control. Furthermore, Eif4ebp1 deletion accelerated β cell loss and exacerbated hyperglycemia in mouse models of diabetes. Thus, 4E-BP1 induction contributes to the maintenance of β cell homeostasis during ER stress and is a potential therapeutic target for diabetes.

Original languageEnglish
Pages (from-to)269-276
Number of pages8
JournalCell Metabolism
Volume7
Issue number3
DOIs
Publication statusPublished - 2008 Mar 5

Keywords

  • HUMDISEASE
  • PROTEINS
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress'. Together they form a unique fingerprint.

  • Cite this

    Yamaguchi, S., Ishihara, H., Yamada, T., Tamura, A., Usui, M., Tominaga, R., Munakata, Y., Satake, C., Katagiri, H., Tashiro, F., Aburatani, H., Tsukiyama-Kohara, K., Miyazaki, J. I., Sonenberg, N., & Oka, Y. (2008). ATF4-Mediated Induction of 4E-BP1 Contributes to Pancreatic β Cell Survival under Endoplasmic Reticulum Stress. Cell Metabolism, 7(3), 269-276. https://doi.org/10.1016/j.cmet.2008.01.008