Quantification of D -Amino Acids in Type 1 Diabetes-Affected Human Serum

Recent advances in understanding the roles of d-amino acids (d-AAs) in nervous and endocrine systems have highlighted their emerging significance in cell-to-cell signaling, particularly in diabetes, where d-AAs are localized in specific islet cell types. In type 1 diabetes (T1D), the autoimmune-mediated destruction of β-cells and the consequent reduction of insulin production impact the disease onset and progression. The presence of d-AAs in T1D serum allows us to understand if they are misregulated in T1D. Correlations between serum d-AAs, glycated hemoglobin (HbA1c), C-peptide levels, and disease duration in T1D patients are investigated. d/l-alanine, -proline, -aspartate, -serine, and -glutamate are quantified using chiral liquid chromatography-tandem mass spectrometry with a multiple-reaction-monitoring approach (LC-MRM-MS/MS). Additionally, d-cysteine levels are determined through a luciferase assay and confirmed via d-amino acid oxidase enzyme degradation. Positive correlations between d-glutamate and d-aspartate levels and C-peptide levels are observed. Obtained results demonstrate positive correlations between d-alanine, d-proline, and d-cysteine levels and disease duration, and a negative correlation with d-aspartate and d-glutamate. These findings suggest the involvement of a range of d-AAs and that serum d-AA levels may be indicators of T1D progression.