Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus
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RESEARCH ARTICLE
Relationship between guanosine triphosphate pathway and tetrahydrobiopterin in gestational diabetes mellitus Songül Ünüvar 1
&
Rauf Melekoğlu 2 & Emine Şalva 3 & Ceren Acar 4 & Şeyma Yaşar 5
Received: 20 June 2020 / Revised: 31 August 2020 / Accepted: 8 October 2020 # Springer Nature Switzerland AG 2020
Abstract Purpose The present study assesses the change in tetrahydrobiopterin (BH4), one of the most important products in the guanosine triphosphate (GTP) pathway and in other parameters that might affect nitric oxide (NO) production, in gestational diabetes mellitus (GDM). Methods The study included 100 healthy pregnant women and 100 women diagnosed with GDM. Serum levels of neopterin, BH4 and NO were measured. The levels of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GCHI/GTPCH) gene expression were determined. Results It was found that diabetes led to an increase in neopterin and NO levels, and a decrease in BH4 levels. A stimulation was observed in eNOS gene expression in the GDM group when compared to the control group, while GCHI levels were found to decrease when compared to the control group. iNOS gene expression was detected in neither the healthy controls nor the patient group. Conclusions Decreased NO bioavailability plays an important role in the progression of such macrovascular diseases as diabetes. BH4 levels decrease in diabetes patients, while the increased gene expression of GCHI reverses the diabetes-related BH4 deficiency and allows the endothelial cells to regain their ability to produce NO. Since GCHI is the rate-limiting enzyme in the biosynthesis of BH4, changes in GCHI levels directly affect the BH4 levels and the NO metabolism, leading to an increased risk of macrovascular complications. The significant increase in neopterin levels suggest that this is a potential biomarker for the early diagnosis of GDM. Keywords Neopterin . Gestational Diabetes Mellitus . Guanosine Triphosphate Pathway . Tetrahydrobiopterin
Introduction The relationship between GTP pathway and BH4 has been evaluated in several studies, and particularly in studies of
* Songül Ünüvar [email protected] 1
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, İnönü University, Malatya, Turkey
2
Department of Obstetrics and Gynecology, Faculty of Medicine, İnönü University, Malatya, Turkey
3
Department of Pharmaceutical Biotechnolog, Faculty of Pharmacy, İnönü University, Malatya, Turkey
4
Department of Molecular Biology and Genetics, Faculty of Arts & Science, İnönü University, Malatya, Turkey
5
Department of Biostatistics and Medical Informatics, Faculty of Medicine, İnönü University, Malatya, Turkey
neurological diseases. To date, however, the basis of this relationship has not been clearly defined in vascular diseases such as diabetes. Diabetes (diabetes mellitus) is a metabolic disease that is characterized by hyperglycemia, which occurs due to a disturbance in insulin secretion, insulin res
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