| Literature DB >> 32376799 |
Ayumi Kanno1, Shun-Ichiro Asahara1, Ayuko Furubayashi2, Katsuhisa Masuda2, Risa Yoshitomi2, Emi Suzuki1, Tomoko Takai1, Maki Kimura-Koyanagi1, Tomokazu Matsuda1, Alberto Bartolome3, Yushi Hirota1, Norihide Yokoi4, Yuka Inaba5, Hiroshi Inoue5, Michihiro Matsumoto6, Kenichi Inoue7, Takaya Abe7,8, Fan-Yan Wei9, Kazuhito Tomizawa9, Wataru Ogawa1, Susumu Seino4, Masato Kasuga10, Yoshiaki Kido1,2.
Abstract
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.Entities:
Keywords: Endocrinology; Insulin signaling; Islet cells; Metabolism
Mesh：
Substances：
Year: 2020 PMID： 32376799 PMCID： PMC7253016 DOI： 10.1172/jci.insight.128820
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708