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Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research

Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct m...

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Autores principales: Bala, Cornelia G., Rusu, Adriana, Ciobanu, Dana, Bucsa, Camelia, Roman, Gabriela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071553/
https://www.ncbi.nlm.nih.gov/pubmed/33921149
http://dx.doi.org/10.3390/antiox10040610
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author Bala, Cornelia G.
Rusu, Adriana
Ciobanu, Dana
Bucsa, Camelia
Roman, Gabriela
author_facet Bala, Cornelia G.
Rusu, Adriana
Ciobanu, Dana
Bucsa, Camelia
Roman, Gabriela
author_sort Bala, Cornelia G.
collection PubMed
description Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1–Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism.
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spelling pubmed-80715532021-04-26 Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research Bala, Cornelia G. Rusu, Adriana Ciobanu, Dana Bucsa, Camelia Roman, Gabriela Antioxidants (Basel) Article Oxidative stress plays a key role in the development of chronic diabetes-related complications. Previous metabolomic studies showed a positive association of diabetes and insulin resistance with branched-chain amino acids (AAs) and aromatic AAs. The purpose of this research is to identify distinct metabolic changes associated with increased oxidative stress, as assessed by nitrotyrosine levels, in type 2 diabetes (T2DM). Serum samples of 80 patients with insulin-treated T2DM are analyzed by AA-targeted metabolomics using ultrahigh-performance liquid chromatography/mass spectrometry. Patients are divided into two groups based on their nitrotyrosine levels: the highest level of oxidative stress (Q4 nitrotyrosine) and lower levels (Q1–Q3 nitrotyrosine). The identification of biomarkers is performed in MetaboAnalyst version 5.0 using a t-test corrected for false discovery rate, unsupervised principal component analysis and supervised partial least-squares discriminant analysis (PLS-DA). Four AAs have significantly different levels between the groups for highest and lower oxidative stress. Cysteine, phenylalanine and tyrosine are substantially increased while citrulline is decreased (p-value <0.05 and variable importance in the projection [VIP] >1). Corresponding pathways that might be disrupted in patients with high oxidative stress are phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, phenylalanine metabolism, cysteine and methionine metabolism and tyrosine metabolism. MDPI 2021-04-15 /pmc/articles/PMC8071553/ /pubmed/33921149 http://dx.doi.org/10.3390/antiox10040610 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bala, Cornelia G.
Rusu, Adriana
Ciobanu, Dana
Bucsa, Camelia
Roman, Gabriela
Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
title Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
title_full Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
title_fullStr Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
title_full_unstemmed Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
title_short Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research
title_sort amino acid signature of oxidative stress in patients with type 2 diabetes: targeted exploratory metabolomic research
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071553/
https://www.ncbi.nlm.nih.gov/pubmed/33921149
http://dx.doi.org/10.3390/antiox10040610
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