Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Recently published
    • Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Recently published
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising/recruitment
  • Contact
GCN2 regulates pancreatic β cell mass by sensing intracellular amino acid levels
Ayumi Kanno, … , Masato Kasuga, Yoshiaki Kido
Ayumi Kanno, … , Masato Kasuga, Yoshiaki Kido
Published May 7, 2020
Citation Information: JCI Insight. 2020;5(9):e128820. https://doi.org/10.1172/jci.insight.128820.
View: Text | PDF
Research Article Endocrinology Metabolism

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

  • Text
  • PDF
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.

Authors

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 Ogawa, Susumu Seino, Masato Kasuga, Yoshiaki Kido

×

Figure 1

Carriers of the risk allele for EIF2AK4 SNP rs2250402 exhibit reduced insulin secretion but no change in insulin sensitivity.

Options: View larger image (or click on image) Download as PowerPoint
Carriers of the risk allele for EIF2AK4 SNP rs2250402 exhibit reduced in...
(A) Insulinogenic index determined during a 75-g oral glucose tolerance test (OGTT) for the study participants classified according to normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes mellitus (T2DM) status and whether they harbored the risk allele (C) of rs2250402. (B and C) First-phase insulin secretion and the disposition index, respectively, determined for the study subjects during a glucose clamp test. Data in A–C are the mean ± SEM. *P < 0.05 (2-tailed Student’s t test). (D and E) Correlation between the disposition index and BMI for the study participants with NGT (D) or IGT (E). Data in D and E were analyzed by Pearson’s correlation analysis. In D, the dotted line shows the regression line of AC + CC. IRI, immunoreactive insulin.
Follow JCI Insight:
Copyright © 2021 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts