| First Author | Kanno A | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 9 | PubMed ID | 32376799 |
| Mgi Jnum | J:301914 | Mgi Id | MGI:6505348 |
| Doi | 10.1172/jci.insight.128820 | Citation | Kanno A, et al. (2020) GCN2 regulates pancreatic beta cell mass by sensing intracellular amino acid levels. JCI Insight 5(9) |
| abstractText | 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 beta cell mass. Our data suggest that GCN2 senses amino acid deficiency in beta cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent beta cell failure during the consumption of a high-fat diet. |
