GCN2 regulates pancreatic ß cell mass by sensing intracellular amino acid levels.
JCI Insight
; 5(9)2020 05 07.
Article
em En
| MEDLINE
| ID: mdl-32376799
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 ß cell mass. Our data suggest that GCN2 senses amino acid deficiency in ß cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent ß cell failure during the consumption of a high-fat diet.
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MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
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Diabetes Mellitus Tipo 2
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Células Secretoras de Insulina
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Aminoácidos
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Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article