Amino Acid Signature of Oxidative Stress in Patients with Type 2 Diabetes: Targeted Exploratory Metabolomic Research.
Cornelia G BalaAdriana RusuDana Mihaela CiobanuCamelia BucsaGabriela RomanPublished in: Antioxidants (Basel, Switzerland) (2021)
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.
Keyphrases
- oxidative stress
- type diabetes
- amino acid
- mass spectrometry
- glycemic control
- dna damage
- liquid chromatography
- insulin resistance
- ischemia reperfusion injury
- diabetic rats
- induced apoptosis
- cardiovascular disease
- machine learning
- nitric oxide
- metabolic syndrome
- high fat diet
- magnetic resonance
- cancer therapy
- small molecule
- magnetic resonance imaging
- high resolution mass spectrometry
- heat shock
- gas chromatography
- risk factors
- drug delivery
- adipose tissue
- patient reported outcomes
- drug induced
- fluorescent probe
- signaling pathway
- computed tomography
- single molecule
- resting state
- psychometric properties
- living cells
- patient reported