Back to Search
Start Over
Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.
- Source :
-
Cellular & Molecular Life Sciences . Jan2024, Vol. 81 Issue 1, p1-15. 15p. - Publication Year :
- 2024
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1420682X
- Volume :
- 81
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cellular & Molecular Life Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 174772725
- Full Text :
- https://doi.org/10.1007/s00018-023-05082-2