糖尿病小肠上皮细胞葡萄糖转运体2（GLUT2）功能异常可能是糖尿病餐后血糖持续增高的重要原因之一。小檗碱（Berberine, BBR）具有降糖、降脂等多种生物学效应。课题组以往发现小檗碱激活细胞胰岛素受体、胰岛素样生长因子信号通路改善血管及心脏功能，但降血糖的机制不清。预实验发现，小檗碱抑制糖尿病小鼠小肠上皮细胞刷状缘GLUT2转位，调控机制可能与小檗碱下调小肠上皮细胞IGF-1R—PLC-beta2信号途径有关。由此我们提出“小檗碱通过IGF-1R—PLC-beta2—GLUT2信号通路抑制糖尿病小鼠小肠上皮GLUT2转位”，这一科学假说。利用小动物PET-CT、葡萄糖钳夹、离体小肠灌流及葡萄糖转运测量等多种实验技术，分别在糖尿病小鼠动物模型上通过整体、离体小肠、小肠上皮细胞及小肠上皮细胞IGF-1R敲除小鼠探讨小檗碱对糖尿病小肠上皮葡萄糖转运的影响及其机制。

Postprandial hyperglycemia is a determinant causative factor in early type 2 diabetes mellitus. Pathological lesion of translocation and internalization of glucose transporter 2 (GLUT-2) in diabetic intestinal epithelium could lead to permanent localization of GLUT-2 in the brush border membrane, which is the major reason why postprandial hyperglycemia occurs in T2DM. Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose and regulating lipid metabolism. But the mechanism of berberine lowering glucose and the alleviated the compliance of the diabetes is still elusive. Our previous study shows that berberine improves diabetic cardiovascular system insulin sensitivity by up-regulating insulin receptor and IGF-1R-mediated signaling pathway in diabetic rats. And our preliminary data shows that berberine inhibited isolated perfused intestinal glucose translate and the expression of GLUT2 on the brush border membrane. Therefore, we hypothesis whether berberine decreased GLUT2 internalization of intestinal brush border epithelium of diabetic mouse according IGF-1R-PLC-beta2-GLUT2 mediated signaling. Using PET-CT, Hyperinsulinemic-Euglycemic Clamps and intestinal epithelial IGF-1R knockout mice (IE-IGF1RKO), the mechanism of berberine alleviated diabetic intestinal brush border epithelium GLUT2 transformation were studied.