胰岛素抵抗是妊娠期糖尿病的重要发病机制，其原因与胎盘密切相关，但具体机制尚不明确。我们的前期研究表明，妊娠期糖尿病胎盘上高表达的14-3-3蛋白等可影响胰岛素信号通路；而新近研究表明，胎盘可以分泌外泌体影响全身。——由此，我们提出，妊娠期糖尿病胎盘上影响胰岛素信号通路的因子是否通过外泌体导致全身胰岛素抵抗？本项目拟（1）在分子水平，检测妊娠期糖尿病胎盘外泌体内含蛋白（尤其与胰岛素抵抗相关的14-3-3蛋白等）；（2）在细胞水平，评估胎盘外泌体对血管内皮、脂肪和肌肉细胞胰岛素信号通路（IRS/PI3K/pAKT）及其后续糖(GSK3/GS/PFKFB2/AS160)、脂代谢(SREBP/PKA/HSL)通路的影响；（3）在整体水平，研究胎盘外泌体水平和全身胰岛素抵抗状态的关系。从而明确胎盘中影响胰岛素信号通路的因子通过外泌体作用全身，导致胰岛素抵抗的机制，为妊娠期糖尿病发病机制和早期预测提供

Insulin resistance is the important etiology of gestational diabetes mellitus(GDM). Insulin resistance is associated with placentation, but the underline mechanism has not been clarified. We have found many proteins(e.g. 14-3-3 proteins) upregulated in GDM placenta may affect insulin signal pathway; and recent research show that, placenta impact the maternal body by releasing exosome. Therefore, we presume that, placenta-derived exosomes may carry proteins that will affect insulin pathway to maternal body and induce insulin resistance. To resolve this question, we will: (1)on molecular level, study the proteomics of placenta-derived exosomes, especially those associated with insulin resistance (e.g. 14-3-3 proeteins);(2)on cellular and functional aspects, evaluate the impact of placenta-derived exosomes on insulin signal pathway(IRS/PI3K/pAKT), and downstream glucose(GSK3/GS/PFKFB2/AS160) and lipid(SREBP/PKA/HSL) pathway in venous endothelial cells, adipose cells and muscle cells; (3)in metabolic status of the whole body, research the level of placenta-derived exosomes and insulin resistance. By demonstrating the effect of placenta-derived exosomes on insulin resistance, this study will serve for the understanding of GDM mechanism and early diagnosis.