肠上皮组织与2型糖尿病及胰岛素抵抗的发生发展密切相关。项目在已获得结构明确的浒苔寡糖，并证实其具有显著降血糖和改善胰岛素抵抗作用基础上，以肠上皮细胞为切入点，利用差异蛋白质组学分析技术，研究浒苔寡糖调控肠上皮细胞胰岛素受体及下游信号转导通路，及其改善胰岛素抵抗的作用机制。项目拟以胰岛素抵抗大鼠为模型，结合药理学和病理学指标，通过基于2-DE和iTRAQ相结合的蛋白质组学技术，对模型大鼠肠上皮细胞进行多靶点分析，深入研究浒苔寡糖对模型大鼠肠上皮细胞胰岛素MEK/ERK和PI3K/AKT信号通路的影响，以及改善大鼠胰岛素抵抗的基因表达谱及靶点基因。综合以上研究，揭示基于蛋白质组学的肠上皮细胞与改善胰岛素抵抗的关联性，阐明浒苔寡糖改善胰岛素抵抗的整体分子效应机制，为有效防治2型糖尿病的海洋创新药物及营养功能性产品的研发提供理论依据和技术支撑。

Intestinal epithelial tissue is closely related to the occurrence and development of type 2 diabetes mellitus (T2DM) and insulin resistance. Based on the previous discoveries of Enteromorpha prolifera oligosaccharide (EPO) do having hypoglycemic effects and improving of insulin resistance, this project will investigate the action mechanisms of EPO on regulating insulin signal transduction pathways and T2DM insulin resistance based on intestinal epithelial cells (IECs) as target, combined proteomics with advanced data mining technologies in bioinformatics. In this project, T2DM insulin resistant rats will be used as the animal model system. Based on the pharmacological and pathological characterization of EPO treated rats, meta-proteomics based on combination of two-dimensional polyacrylamide gel electrophoresis (2-DE) and isobaric tags for relative and absolute quantitation (iTRAQ) will be used to analyze the IECs of rats. This allows us to further reveal the gene expression profiles and the target genes of IECs with the improvement of T2DM insulin resistance by EPO. Over above studies, this project will explain the relationship between the changes of MEK/ERK and PI3K/AKT signaling pathways of IECs by EPO and the improvement of insulin resistance. Also, the project will establish the overall mechanism of improvement of T2DM insulin resistance with EPO. In summary, this study will provide the theoretical basis and technical support for the development of marine algal anti-T2DM drug and its natural health care products.