2型糖尿病并发非酒精性脂肪肝简称2型糖尿病NAFLD, 其主要特征有空腹血糖和TG升高，肝脏脂肪积聚。近年发现SIK1通过磷酸化CRTC2影响空腹血糖，磷酸化SREBP-1c影响肝脏脂质合成，SIK1信号通路在糖尿病糖脂代谢紊乱和脂肪肝形成方面起着重要作用。我们近期的研究显示2型糖尿病NAFLD大鼠的肝脏和高糖培养的肝细胞SIK1表达降低，我们的临床验方贞清方及方中女贞子对2型糖尿病NAFLD大鼠的肝脏脂肪病变有明显的减轻作用，贞清方可上调肝脏SIK1的表达，但其机制有待深入研究。本项目拟采用分子生物学和实验免疫学等技术，研究SIK1/CRTC2和SIK1/SREBP-1c两条信号通路在2型糖尿病NAFLD发病过程中的作用；并研究中药复方贞清方及女贞子的有效成分齐墩果酸对SIK1信号通路的调节作用。本项目对糖尿病NAFLD的发病机制提出新的见解，为中药治疗2型糖尿病NAFLD提供新的靶点。

Type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease (NAFLD) is called NAFLD of type 2 diabetes. Its main features are elevated fasting glucose and triglyceride (TG), fat accumulation in the liver. Recent studies found that salt inducible kinase 1 (SIK1) affected fasting blood glucose and hepatic lipid synthesis by phosphorylated CRTC2 and SREBP-1c respectively. Thus the SIK1 signaling pathway plays an important role in disorder of glucose and lipid metabolism and fatty liver in diabetes mellitus. Our recent studies showed that SIK1 expression is reduced in the liver of NAFLD in type 2 diabetic rats and hepatocytes cultured in high glucose. Our clinical prescription Zhenqing Recipe and Fructus Ligustri Lucidi in Zhenqing Recipe significantly alleviated NAFLD of type 2 diabetes rats. We also observed that Zhenqing Recipe could upregulate the expression of SIK1 in the liver, but its mechanism needs further study. We intend to study the role and the mechanism of SIK1/CRTC2 and SIK1/SREBP-1c signaling pathways in the pathogenesis of NAFLD in type 2 diabetes rats and high glucose cultured liver cells by using molecular biological and immunological technology， and also study the effect of Zhenqing Recipe and Oleanolic acid on regulating SIK1 signaling pathways. This project puts forward new insights for the pathogenesis of diabetic NAFLD, and provides new target for traditional Chinese medicine in the treatment of NAFLD in type 2 diabetes.