RESUMO
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-κB (NF-κB) 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-κB 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 (P=0.024), TLR4 (P=0.037), STAT1 (P=0.027), and CX3CL1 (P=0.017) mRNA expression, whereas the GDM2 group showed markedly lower TNFRSF1A (P=0.042), PPARG (P=0.018), STAT3 (P=0.013), and CX3CL1 (P=0.038) 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 (P=0.01), HOMA-IR (P=0.004), and TLR2 mRNA expression (P=0.04), as well as lower ISSI2 (P=0.01) and disposition indices, DI30 (P=0.03) and DI120 (P=0.01), 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.
Assuntos
Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Regulação da Expressão Gênica , Leucócitos Mononucleares/metabolismo , Subunidade p50 de NF-kappa B/sangue , Receptor 2 Toll-Like/metabolismo , Adulto , Glicemia/análise , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/metabolismo , Diabetes Gestacional/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Resistência à Insulina , Subunidade p50 de NF-kappa B/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , RNA Mensageiro/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
The suppressor of cytokine signaling (SOCS) proteins are feedback inhibitors of signaling pathways induced by cytokines, hormones and growth factors. In the present study we measured the expression of SOCS1, SOCS3, interleukin-6 (IL-6), IL-6 receptor, IL-8 and leptin mRNA in paired samples of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from 18 pregnant women with normal glucose tolerance (NGT) and 20 subjects with gestational diabetes mellitus (GDM), using quantitative RT-PCR. The patients with GDM had significantly higher IL-8 mRNA expression in VAT than the women with NGT (p = 0.007), whereas the expression of SOCS1, SOCS3 and other genes study did not differ significantly between the two groups. Stepwise regression analysis revealed that SOCS1 mRNA expression in VAT was significantly associated with prepregnancy BMI (ß = -0.68, p = 0.03) and IL-8 mRNA expression (ß = 0.66, p = 0.03), whereas SOCS3 mRNA expression in VAT was independently predicted by IL-6 mRNA expression (ß = 0.94, p = 0.0002, R(2) = 0.88). In conclusion, our results did not show significant differences in SOCS1 and SOCS3 mRNA expression in adipose and placental tissue obtained from pregnant women with and without GDM.