GCN2 regulates pancreatic β cell mass by sensing intracellular amino acid levels

Ayumi Kanno, Shun Ichiro Asahara, Ayuko Furubayashi, Katsuhisa Masuda, Risa Yoshitomi, Emi Suzuki, Tomoko Takai, Maki Kimura-Koyanagi, Tomokazu Matsuda, Alberto Bartolome, Yushi Hirota, Norihide Yokoi, Yuka Inaba, Hiroshi Inoue, Michihiro Matsumoto, Kenichi Inoue, Takaya Abe, Fan Yan Wei, Kazuhito Tomizawa, Wataru OgawaSusumu Seino, Masato Kasuga, Yoshiaki Kido

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


EIF2AK4, which encodes the amino acid deficiency-sensing protein GCN2, has been implicated as a susceptibility gene for type 2 diabetes in the Japanese population. However, the mechanism by which GCN2 affects glucose homeostasis is unclear. Here, we show that insulin secretion is reduced in individuals harboring the risk allele of EIF2AK4 and that maintenance of GCN2-deficient mice on a high-fat diet results in a loss of pancreatic β cell mass. Our data suggest that GCN2 senses amino acid deficiency in β cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent β cell failure during the consumption of a high-fat diet.

Original languageEnglish
Article numbere128820
JournalJCI insight
Issue number9
Publication statusPublished - 2020 May 7


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