胰岛素抵抗（IR）是2型糖尿病（T2DM）及多种代谢性疾病发生的共同病理生理基础。然而其发生机制目前仍不清楚。骨形成蛋白-9 （BMP-9）是BMPs家族的成员之一。我们前期在人及动物研究中发现BMP-9与IR和T2DM有关。本课题拟深入研究BMP-9在IR发生和发展中的作用极其分子机制，并探讨其能否成为T2DM治疗的靶标。本研究拟构建BMP-9 基因敲除（BMP-9 KO）和过表达（BMP-9-Tg）小鼠，给予高脂饲养，着力打造遗传和环境因素共同作用，具IR表型的小鼠模型。利用扩展胰岛素钳夹术和糖动力学研究，在体内及细胞水平深入研究BMP-9表达模式改变对糖代谢及胰岛素信号系统的影响，重点探讨BMP-9如何与受体结合进入肝细胞发挥作用，并寻找其功能域。初步勾勒出在BMP-9基因缺陷或过表达和环境因素共同作用的特定条件下，糖代谢紊乱和胰岛素信号调控网络的变化及可能的机制。

Insulin resistance (IR) is the common pathophysiological basis of type 2 diabetes (T2DM) and a variety of metabolic diseases. However, the mechanism of its occurrence is still unclear. Bone morphogenetic protein9 (BMP9) is One of the family members of the BMPs. Our previous studies in human and animal have found that BMP-9 is related to IR and T2DM. The aim of this study is to construct BMP-9 knockout (BMP-9 KO) and overexpressing (BMP-9-Tg) mice, which is fed by high-fat diet (combined genetic and environmental factors), create a mouse model with IR phenotype. By using the extended insulin clamp technique and glucose kinetics, we’ll study of the effects of the BMP-9 expression on glucose metabolism and insulin signal system in cell and in vivo. We will focus on our attention about how BMP-9 combines with the receptor into the liver cells to play a role and to find its functional domain. The changes and possible mechanisms of glycometabolism disorder and insulin signal regulation network are preliminarily outlined under specific conditions of BMP-9 gene deficiency or over expression and environmental factors. It provides valuable data and data for finding the molecular biological targets of IR.