Abstract
AimDevelopment of type 2 diabetes (T2DM) is associated with disturbances in immune and metabolic status that may be reflected by an altered gene expression profile of peripheral blood mononuclear cells (PBMC). To reveal a potential family predisposition to these alterations, we investigated the regulation of gene expression profiles in circulating CD14+ and CD14- PBMC in fasting conditions and in response to oral glucose tolerance test (OGTT) in glucose tolerant first-degree relatives (FDR) of T2DM patients and in control subjects.Materials and MethodsThis work is based on the clinical study LIMEX (NCT03155412). Non-obese 12 non-diabetic (FDR), and 12 control men without family history of diabetes matched for age and BMI underwent OGTT. Blood samples taken before and at the end of OGTT were used for isolation of circulating CD14+ and CD14- PBMC. In these cells, mRNA levels of 94 genes related to lipid and carbohydrate metabolism, immunity, and inflammation were assessed by qPCR.ResultsIrrespectively of the group, the majority of analyzed genes had different mRNA expression in CD14+ PBMC compared to CD14- PBMC in the basal (fasting) condition. Seven genes (IRS1, TLR2, TNFα in CD14+ PBMC; ABCA1, ACOX1, ATGL, IL6 in CD14- PBMC) had different expression in control vs. FDR groups. OGTT regulated mRNA levels of nine genes selectively in CD14+ PBMC and of two genes (ABCA1, PFKL) selectively in CD14-PBMC. Differences in OGTT-induced response between FDR and controls were observed for EGR2, CCL2 in CD14+ PBMC and for ABCA1, ACOX1, DGAT2, MLCYD, and PTGS2 in CD14- PBMC.ConclusionThis study revealed a different impact of glucose challenge on gene expression in CD14+ when compared with CD14- PBMC fractions and suggested possible impact of family predisposition to T2DM on basal and OGTT-induced gene expression in these PBMC fractions. Future studies on these putative alterations of inflammation and lipid metabolism in fractionated PBMC in larger groups of subjects are warranted.
Highlights
Type 2 diabetes mellitus (T2DM) is associated with a number of disturbances of immune status and metabolic pathways [1] that can be detected in insulin sensitive tissue and in accessible peripheral blood mononuclear cells (PBMC)
In this study we investigated the impact of family history of T2DM on mRNA gene expression in circulating CD14+ and CD14- PBMC in the fasting conditions and in response to OGTT
Our study suggested that several genes could have different basal expression and/or could be differentially regulated in response to OGTT in first-degree relatives (FDR) when compared to controls, in agreement with several previous studies showing that the changes of gene expression in PBMC
Summary
Type 2 diabetes mellitus (T2DM) is associated with a number of disturbances of immune status and metabolic pathways [1] that can be detected in insulin sensitive tissue and in accessible peripheral blood mononuclear cells (PBMC). PBMC from patients with T2DM have shown alterations in mRNA levels of genes involved in the regulation of inflammation, lipid and glucose metabolism, and several signaling pathways [2,3,4,5]. It might be hypothesized that alterations in gene expression are present already in non-obese individuals with genetic predisposition to T2DM, such as FDR. A number of genes with dysregulated expression was found in FDR when compared with subjects without T2DM in antecedence, including adiponectin in adipose tissue [8] and genes involved in insulin signaling and fatty acid metabolism in skeletal muscle [9, 10]. PBMC proved to be a good surrogate marker of systemic and adipose tissue metabolic state [11, 12], they represent a mixture of cell types with considerably different roles, behavior and metabolism, i.e. monocytes, dendritic cells and lymphocytes [13] and analysis of PBMC population in whole may limit the interpretation of results
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