ArticleNature communications2022
Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 2 of them syntheses that pooled it.
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Who cites it
68 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years.Journal of proteome research · 2025Pooled it
- Association of maternal blood metabolomics and gestational diabetes mellitus risk: a systematic review and meta-analysis.Reviews in endocrine & metabolic disorders · 2025Pooled it
- Effect of SY009, a novel SGLT1 inhibitor, on the plasma metabolome and bile acids in patients with type 2 diabetes mellitus.Frontiers in endocrinology · 2025Trial
- Phenylalanine exacerbates psoriasiform inflammation through NF‑κB‑mediated dendritic cell activation and Th17 polarization.International journal of molecular medicine · 2026Article
- Article
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Metabolic pathways associated with cardiometabolic risk effects on cognition in middle-aged adults: the CARDIA study.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Rapid improvement of renal microcirculatory homeostasis by liraglutide following diabetes induction.Diabetes, obesity & metabolism · 2026Article
- Aminoacyl-tRNA Synthetases: Variant Classification, Functional Assays, and Emerging Therapeutic Strategies.Journal of inherited metabolic disease · 2026Review
- Comparative study on changes in serum amino acid metabolic profiles in mice exposed to perfluorooctanoic acid and sodium ρ-perfluorous nonenoxybenzene sulfonate.Scientific reports · 2026Article
- Metabolomics reveals early pregnancy serum metabolic changes and predictive biomarkers in gestational diabetes mellitus.Nutrition & metabolism · 2026Article
- Impact of obesity on aromatic amino acids and brain glucose during acute hyperglycemia.American journal of physiology. Endocrinology and metabolism · 2026Article
- Faecal microbiome and serum metabolomics: potential biomarkers for type 2 diabetes.BMC microbiology · 2026Article
- Integrated metabolomics analysis identifies distinct amino acid signatures in chronic hepatitis B patients with metabolic dysfunction-associated steatotic liver disease.Frontiers in cellular and infection microbiology · 2026Article
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Progress on hydrogel delivery systems targeting metabolism disorders in the treatment of diabetic foot ulcers.Frontiers in cell and developmental biology · 2026Review
- The mechanisms underlying COVID-19 induced insulin resistance: a narrative review.Frontiers in endocrinology · 2026Review
- Construction and analysis of a developmental RNA editome in adipose tissue of Ningxiang pigs.BMC genomics · 2025Article
- A Novel Single-Test Approach for GDM Diagnosis: Identification and Prediction of High-Risk Postprandial Hyperglycemia.Metabolites · 2025Article
- Metabolomics of saliva, serum, and urine for pathogenesis, diagnosis, and prognosis in gestational diabetes mellitus.Nature communications · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms. Mechanistically, FARS phenylalanylate lysine 1057/1079 of IRβ (F-K1057/1079), inactivating IRβ and preventing insulin from promoting glucose uptake by cells. SIRT1 reverse F-K1057/1079 and counteract the insulin-inactivating effects of hFARS and phenylalanine. F-K1057/1079 and SIRT1 levels in white blood cells from T2D patients are positively and negatively correlated with T2D onset, respectively. Blocking F-K1057/1079 with phenylalaninol sensitizes insulin signaling and relieves T2D symptoms in hFARS-transgenic and db/db mice. These findings shed light on the activation of insulin signaling and T2D progression through inhibition of phenylalanylation.
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