ArticleJCI insight2020
GCN2 regulates pancreatic β cell mass by sensing intracellular amino acid levels.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction.Diabetes & metabolism journal · 2026Article
- Single-cell perturbations decipher ribosomal stress-surveillance regulators in type 2 diabetes.Nature metabolism · 2026Article
- The integrated stress response in pancreatic β-cell failure in diabetes: from molecular mechanisms to precision therapeutics.Frontiers in endocrinology · 2026Review
- The Integrated Stress Response in Pancreatic Development, Tissue Homeostasis, and Cancer.Gastroenterology · 2024Review
- Targeting β-Cell Plasticity: A Promising Approach for Diabetes Treatment.Current issues in molecular biology · 2024Review
- Inhibition of asparagine synthetase effectively retards polycystic kidney disease progression.EMBO molecular medicine · 2024Article
- Emerging Role of GCN1 in Disease and Homeostasis.International journal of molecular sciences · 2024Review
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Chlorogenic Acid and Caffeine in Coffee Restore Insulin Signaling in Pancreatic Beta Cells.The Kobe journal of medical sciences · 2023Article
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Genetic and Pharmacological Inhibition of GCN2 Ameliorates Hyperglycemia and Insulin Resistance in Type 2 Diabetic Mice.Antioxidants (Basel, Switzerland) · 2022Article
- GPRC6A Mediates Glucose and Amino Acid Homeostasis in Mice.Metabolites · 2022Article
- GCN2: roles in tumour development and progression.Biochemical Society transactions · 2022Review
- Regulation of Pancreatic β-Cell Mass by Gene-Environment Interaction.Diabetes & metabolism journal · 2022Review
- Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies.BMJ open diabetes research & care · 2022Article
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- Roles of interacting stress-related genes in lifespan regulation: insights for translating experimental findings to humans.Journal of translational genetics and genomics · 2021Article
Corrections and comments
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Authors and funding
23 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.