妊娠期糖尿病通过其不良宫内环境影响胎儿健康，而胎盘胰岛素信号通路受损引起胎盘代谢异常是不良宫内环境的关键成因。我们的前期研究表明，14-3-3蛋白在妊娠期糖尿病胎盘高表达；而14-3-3蛋白和胰岛素信号通路若干关键蛋白有相互作用，但对胰岛素信号通路的调节方式尚不明确。因此，本项目拟进一步研究14-3-3蛋白对胎盘胰岛素信号通路的调控机制。本研究将在妊娠期糖尿病胎盘滋养细胞和血管内皮细胞中，研究14-3-3蛋白和胰岛素信号通路关键蛋白 (IR/IRS/PI3K/AKT)的相互作用；在过表达/沉默条件下，分析14-3-3蛋白对上述蛋白表达、磷酸化、亚细胞定位的影响；并结合临床资料，探讨胎盘14-3-3蛋白表达和母儿胰岛素抵抗的关系，以论证14-3-3蛋白高表达导致妊娠期糖尿病胎盘胰岛素信号受损的假说，为临床上通过改善胰岛素抵抗，优化宫内环境，降低子代并发症，提高人口质量提供科学依据。

Gestational diabetes mellitus (GDM) impacts both long and short term health of offspring via its adverse intrauterine environment. Insulin signal pathway impairment in placenta may induce metabolic disorders, and thereby plays an important role in the adverse intrauterine environment. Our recent findings have shown 14-3-3 protein is up-regulated in GDM placenta, and 14-3-3 protein can interact with several key proteins of insulin signal pathway; however, the pattern and outcome of the interaction is unclear currently. Therefore, the primary purpose of the present project is to uncover the mechanism by which 14-3-3 protein regulates insulin signal pathway in GDM placenta. Firstly, we will compare the expressions and interactions of 14-3-3 protein and insulin signal pathway related proteins (IR/ IRS/ PI3K/ AKT) in GDM and normal placental cells. Furthermore, we will investigate the protein expression, phosphorylation, and subcellular location of insulin signal pathway related proteins in case of 14-3-3 protein overexpression or knockdown. Additionally, based on our large cohort and sample bank, we will study the relationship between 14-3-3 protein placental expression and insulin resistance in both mother and fetus. By testing the hypothesis that 14-3-3 protein impairs insulin signal pathway in GDM placenta, the current project will provide scientific evidence for reducing offspring complications by improving insulin resistance and optimizing intrauterine environment in clinic.