The expression of genes involved in NF-κB activation in peripheral blood mononuclear cells of patients with gestational diabetes

Abstract

Objective: In patients with obesity and type 2 diabetes, the changes in insulin resistance are associated with the changes in expression of genes involved in nuclear factor-kB (NF-kB) activation in peripheral blood mononuclear cells (PBMCs). As such studies have never been carried out in patients with gestational diabetes (GDM), in this study, we evaluated the expression of genes involved in NF-kB activation and related to glucose metabolism in PBMCs obtained from pregnant women with GDM and normal glucose tolerance (NGT). Design and methods: RT-PCR was performed in 60 pregnant women divided into three groups: GDM at the 1st visit, i.e. in the 24th-28th weeks of gestation (GDM1), NGT at the first visit and GDM in the 29th-32nd weeks (GDM2), and NGT at both visits. The tests were repeated 3 months postpartum. Results: The GDM1 group had significantly higher TLR2 (PZ0.024), TLR4 (PZ0.037), STAT1 (PZ0.027), and CX3CL1 (PZ0.017) mRNA expression, whereas the GDM2 group showed markedly lower TNFRSF1A (PZ0.042), PPARG (PZ0.018), STAT3 (PZ0.013), and CX3CL1 (PZ0.038) mRNA expression in comparison with the NGT group. The women with NGT at the 1st visit who later developed GDM had significantly higher fasting glucose (PZ0.01), HOMA-IR (PZ0.004), and TLR2 mRNA expression (PZ0.04), as well as lower ISSI2 (PZ0.01) and disposition indices, DI 30 (PZ0.03) and DI 120 (PZ0.01), than had the women who remained normoglycemic. Conclusions: Our results suggest that elevated TLR2 expression, as well as higher fasting glucose and lower compensation for increased insulin resistance, may represent early metabolic disturbances in the development of GDM.

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes

“…In contrast to these findings, no statistically significant difference in serum fractalkine levels is found between patients with Type 2 diabetes and control subjects in another study . Moreover, there is no significant difference in fractalkine levels in a pilot study comprising of 12 women with gestational diabetes diagnosed during the second trimester compared with 27 healthy pregnant control subjects and 21 women who developed gestational diabetes during the third trimester of pregnancy . In addition, the β‐cell function marker HOMA‐B is not associated with fractalkine in our cohort.…”

Molecular pathways disrupted by gestational diabetes mellitus

“…Interestingly, TLR2 mRNA expression is increased in PBMCs obtained from the pregnant women who were normoglycaemic at the time of sampling but later developed GDM (Kuzmicki et al 2013). Further, elevated PBMC, TLR2 and TLR4 mRNA expression was evident in GDM in the second trimester; however, 4 weeks later, the difference was not significant, probably as a result of an increase in TLR expressions in the healthy pregnant women (Kuzmicki et al 2013). On the other hand, another study reported that TLR4 mRNA expression was significantly higher in maternal monocytes of patients with GDM obtained after 37 weeks gestation (Xie et al 2014).…”

Astragaloside IV alleviates placental oxidative stress and inflammation in GDM mice

“…In addition, TLR4, as well as its downstream NF-κB signaling pathway, is involved in several physiological and pathological processes and regulates a wide range of diseases, particularly inflammation-related diseases such as GDM ( 25 , 26 , 27 , 28 ). In patients with GDM, the expression of TLR4 was increased in the peripheral blood mononuclear cells, with the activation of NF-κB signaling pathway as well as hyperglycemia and insulin resistance, and all of these factors participated in the development of GDM.…”