Evaluation of pteridins and related pathways in diabetes

Gurcu, S., Evaluation of Pteridins and Related Pathways in Diabetes, Hacettepe University Institute of Health Sciences Ph.D. Thesis in Pharmaceutical Toxicology, Ankara, 2018. Pteridins are heterocyclic compounds that play a role in normal physiological events, and can be detected in biological fluids and tissues with their derivatives (tetrahydrobiopterin, neopterin, biopterin, and xanthopterin). Diabetes mellitus (diabetes) is a metabolic disease characterized by an excessive increase of glucose level in blood and caused by hereditary and/or environmental factors. Type 1 diabetes is a kind of diabetes, depending on the autoimmune mechanisms, in which insulin is not produced or produced very little in the pancreas. In pathology, T-cell mediated autoimmune response leads to the induction of monocytes and macrophages via pancreas. Induced monocytes/macrophages provide the production of neopterin from guanosine triphosphate (GTP) via GTP cyclohydroxylase enzyme. Besides, interferon-gamma (IFN-γ) induces tryptophan degradation by inducing indolamine-2,3-dioxygenase (IDO) enzyme, one of the rate-limiting step catalyzing enzymes in the kynurenine pathway, which has an important role in tryptophan metabolism. In this thesis, it was aimed to investigate the relationship between neopterin, biopterin, tryptophan and kynurenine levels in diabetes patients and discussing the use of these parameters as early biomarkers in the diagnosis and evaluation of diabetes. For this purpose, neopterin, biopterin, tryptophan and kynurenine levels were measured in diabetes patients (n=68) and healthy control group (n=30). Serum and urine neopterin levels and urine biopterin levels in diabetic patients were higher than the control group but not statistically different (p>0.05). Also serum and urine neopterin concentrations were found to be significantly correlated with each other and the kynurenine/tryptophan ratio (p<0.05). Keywords: pteridin, neopterin, biopterin, kynurenine, diabetes This thesis was supported by Hacettepe University Scientific Research Projects Coordination Unit with the project numbered TBB-2016-11762.