Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.
Cell Mol Life Sci
; 81(1): 25, 2024 Jan 12.
Article
en En
| MEDLINE
| ID: mdl-38212570
ABSTRACT
Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Diabetes Mellitus Tipo 2
Límite:
Animals
/
Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article