Positive Correlation between Enhanced Expression of TLR4/MyD88/NF-κB with Insulin Resistance in Placentae of Gestational Diabetes Mellitus

Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (ppppp pAkt: r = -0.47, p p p p

胰岛素抵抗（Insulin resistance, IR）是妊娠期糖尿病（Gestational diabetes mellitus, GDM）病理生理进程中的关键致病因素。针对参与IR的关键器官（如肝脏与脂肪组织）开展的研究表明，Toll样受体4（Toll-like receptor 4, TLR4）可调控胰岛素敏感性。胎盘作为兼具多重功能的母胎界面，可参与GDM患者IR的发生发展。因此，本研究检测了33例GDM产妇与36例糖耐量正常的健康妊娠产妇的足月胎盘中TLR4/髓系分化因子88（Myeloid Differentiation factor 88, MyD88）/核因子κB（Nuclear Factor kappa-light-chain-enhancer of activated B cells, NF-κB）通路的表达水平，评估了局部与全身IR状态，并进一步明确了胎盘TLR4表达与IR的相关性。TLR4蛋白在足月胎盘的多种细胞中均有表达，尤其富集于绒毛合体滋养层细胞。与正常妊娠组相比，GDM患者胎盘组织中TLR4/MyD88/NF-κB通路的表达水平显著升高（ppppp pAkt: r = -0.47, p p p p）