肝细胞特异性敲除锌指蛋白ZBTB20改善ob/ob小鼠血糖机制的研究

Liver plays an important role in glucose homeostasis. Increased hepatic glucose output is the major factor causing hyperglycemia. ZBTB20 is a transcription factor containing POZ zinc finger protein structure. Our preliminary animal experiments found that ZBTB20-gene-knockout mice show lower glucose levels and enhanced insulin sensitivity while blood glucose levels and glucose tolerance improved in Hepatocyte -specific knockout ZBTB20 with leptin deficient mice model(LZB20 KO-ob/ob) compared with ob/ob mice. The project intends to further analyze the glucose metabolic characteristics in LZB20 KO-ob/ob mice. To study the mechanism of how ZBTB20 hepatocyte-specific knockout improves ob/ob glucose by detecting the changes of critical molecular in hepatic insulin and glucagon signal transduction pathway, and the inflammatory cytokines changes related to hepatic insulin signaling pathway, which will reveal the role of ZBTB20 in the regulation of hepatic glucose metabolism and provide new ideas for prevention and treatment of insulin resistance and type 2 diabetes.

肝脏在血糖稳态中发挥重要作用,肝糖输出增加是造成血糖升高的主要因素之一。ZBTB20是一种含有POZ结构的锌指蛋白结构的转录调节因子，我们前期的动物实验发现ZBTB20基因全身性敲除小鼠表现出低血糖、胰岛素敏感性增强等代谢异常，而在肝细胞ZBTB20特异性敲除伴瘦素缺乏的ob/ob小鼠(LZB20 KO-ob/ob）模型，其空腹血糖和葡萄糖耐量较ob/ob小鼠明显改善。本项目拟在此工作基础上进一步分析LZB20 KO-ob/ob小鼠的糖代谢特征，并通过检测肝脏胰岛素、胰高血糖素信号转导通路关键分子变化和影响肝脏胰岛素信号通路的炎症因子和相关激酶的变化情况，探讨肝细胞ZBTB20基因敲除改善ob/ob小鼠血糖的分子机制和作用靶点，揭示ZBTB20分子在肝脏血糖调节中的作用，为胰岛素抵抗、2型糖尿病的防治提供新思路。