糖尿病与肥胖的发生密切相关已成为危害人类健康的重要问题。近年研究报道上调IGFBP-2可延缓肥胖相关性胰岛素抵抗的发生。基于我们发现胰岛素通过PI3K／mTOR通路调控IGFBP-2表达，IGFBP-2血清浓度与胰岛素敏感性成正相关，对糖脂代谢亦有正调节作用。因此，有必要明确IGFBP-2降调代谢性疾病发生发展的分子机制。我们利用转染技术在动物模型（ob/ob,db/db,HFD-ob）和细胞水平上调IGFBP-2蛋白质的表达。1）拟在上述模型中测定靶组织摄取葡萄糖情况和IGFBP-2对血管内皮细胞舒张功能的影响。2）应用ELISA、PCR、免疫印迹的方法检测IGFBP-2是否能够促进胰岛素受体及下游Akt、GSK3的磷酸化。拟阐明IGFBP-2改善能量代谢的分子机制及对糖尿病并发症主要靶组织的调节作用。本研究意在探寻一个敏感的预告基因，可对糖尿病的发生发展作出预警，为临床防治提供新理念。

Diabetes and the risk of diabetes was significantly associated with an obese status has become a major public health problem in China. Previous studies have pointed that IGFBP-2 could prevent obesity and act against the development of insulin resistance. We have documented that insulin regulates IGFBP-2 expression through the PI3K/mTOR pathway in 3T3-L1 cells, and that IGFBP-2 plasma levels are positively associated with markers of insulin sensitivity and improved glucose and lipid metabolism in obese patients. In this context, there is a need to clarify the molecular mechanism by which IGFBP-2 counteracts the development of metabolic diseases. For this project, we will overexpress IGFBP-2 in animal models of diabetes and obesity (ob/ob, db/db and HFD-od mice) and in different cell lines by transfection, in order to increase plasma IGFBP-2 and its activities in diabetic target tissues. 1) We will measure insulin-stimulated glucose uptake and insulin-regulated vasodilatation in above models. 2) We will test whether IGFBP-2 is able to phosphorylate insulin receptor and its downstream factors (Akt, GSK3), which will be performed by ELISA, RT-qPCR and Western blot, respectively. This will unravel the mechanism of IGFBP-2 improved energy metabolism and help understand the association between IGFBP-2 expression and diabetes complications process. This study is aimed at detecting a sensitive biomarker for diabetic pre-diagnosis and predictor of its prognosis, and also at providing a novel therapy for prevention.