ArticleBiomedicines2022
Incorporation of Oxidized Phenylalanine Derivatives into Insulin Signaling Relevant Proteins May Link Oxidative Stress to Signaling Conditions Underlying Chronic Insulin Resistance.
Article in Biomedicines, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 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
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Expression and role of HSPA5 in environmental toxin-induced neurological disorders.Frontiers in molecular neuroscience · 2026Review
- The Impact of SGLT-2 Inhibitors on Hydroxyl Radical Markers and Diabetic Neuropathy: A Short-Term Clinical Study.Antioxidants (Basel, Switzerland) · 2025Article
- The association between circulating phenylalanine and the temporal risk of impaired insulin markers in gestational diabetes mellitus.Molecular genetics and metabolism reports · 2024Article
- Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1).Cancers · 2024Article
- The relationship between hypoxia and Alzheimer's disease: an updated review.Frontiers in aging neuroscience · 2024Review
- The Common Single Cause of Chronic Multi-Hormonal Resistance in Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
- Diabetes: A Multifaceted Disorder.Biomedicines · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
A link between oxidative stress and insulin resistance has been suggested. Hydroxyl free radicals are known to be able to convert phenylalanine (Phe) into the non-physiological tyrosine isoforms ortho- and meta-tyrosine (o-Tyr, m-Tyr). The aim of our study was to examine the role of o-Tyr and m-Tyr in the development of insulin resistance. We found that insulin-induced uptake of glucose was blunted in cultures of 3T3-L1 grown on media containing o- or m-Tyr. We show that these modified amino acids are incorporated into cellular proteins. We focused on insulin receptor substrate 1 (IRS-1), which plays a role in insulin signaling. The activating phosphorylation of IRS-1 was increased by insulin, the effect of which was abolished in cells grown in m-Tyr or o-Tyr media. We found that phosphorylation of m- or o-Tyr containing IRS-1 segments by insulin receptor (IR) kinase was greatly reduced, PTP-1B phosphatase was incapable of dephosphorylating phosphorylated m- or o-Tyr IRS-1 peptides, and the SH2 domains of phosphoinositide 3-kinase (PI3K) bound the o-Tyr IRS-1 peptides with greatly reduced affinity. According to our data, m- or o-Tyr incorporation into IRS-1 modifies its protein-protein interactions with regulating enzymes and effectors, thus IRS-1 eventually loses its capacity to play its role in insulin signaling, leading to insulin resistance.
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Registered trials
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