The elevated gene expression level of the A2B adenosine receptor is associated with hyperglycemia in women with gestational diabetes mellitus

Abstract

Adenosine receptors denoted by A1 , A2A , A2B , and A3 and encoded by ADORA1, ADORA2A, ADORA2B, and ADORA3 genes, respectively, are adenosine-activated G-protein-coupled receptors that play an important role in obesity and type 2 diabetes mellitus. However, little is known about their significance in gestational diabetes mellitus (GDM). The purpose of this study was to investigate whether there are changes in leukocyte AR expression in GDM patients and whether these alterations are linked to well-known diabetic genes. Leukocytes were isolated from the blood of normal glucose tolerant (NGT; n = 35) and GDM (n = 82) pregnant women, and expression of ARs was determined by a semi-quantitative polymerase chain reaction (PCR). Univariate correlation analysis was performed to investigate associations between expression of ARs and anthropometric and metabolic parameters of patients. Furthermore, the identification of diabetic genes linked to significantly differentiated leukocyte adenosine receptors expression in GDM women was also carried out with the use of the human diabetes RT(2) profiler PCR arrays. ADORA2B mRNA expression was significantly higher in GDM versus NGT pregnant women (p < 0.05), and positively correlated with the glucose level at 1-h 75-g oral glucose tolerance test (OGTT; r = 0.21, p = 0.044). Nineteen diabetic genes linked to leukocyte ADORA2B overexpression associated with hyperglycemia in GDM women were also identified. Maternal leukocyte ADORA2B overexpression is associated with hyperglycemia in GDM subjects, and it is accompanied by complex alterations in the expression of diabetes-related genes involved in insulin action, carbohydrate and lipid metabolism, oxidative stress, and inflammation.