ABSTRACT
ObjectiveTo investigate the mechanism of Zuogui Jiangtang Qinggan prescription （ZJQP） in improving glucose and lipid metabolism in loss of skeletalmuscle-specific insulin-like growth factor-1 receptor function （MKR） mice with type 2 diabetes mellitus （T2DM） and non-alcoholic fatty liver disease （NAFLD）. MethodNAFLD was induced by high-fat diet feeding for 8 weeks in MKR mice， which were randomly divided into model group， metformin group （0.067 g·kg-1）， and ZJQP high and low-dose groups（14.8， 7.4 g·kg-1）. Ten FVB mice of the same age were used as the normal group. After 8 weeks of drug treatment， the oral glucose tolerance test （OGTT） was performed， the serum was taken to detect triacylglycerol （TG） and total cholesterol （TC）， and the wet weight of the mouse liver was weighed. Haematoxylin-eosin （HE） staining and oil red O staining were performed to assess histopathology of liver. The mRNA expression and protein expression of Fork head box protein O1 （FoxO1）， phosphoenolpyruvate carboxykinase （PEPCK）， glucose-6-phosphatase （G6Pase）， and apolipoprotein C3 （ApoC-Ⅲ） in liver tissues were detected by real-time fluorescent quantitative PCR （Real-time PCR） and Western blot， respectively. ResultAs compared with the normal group， the levels of fasting blood glucose， liver index， serum TG， TC， and OGTT of mice in the model group increased significantly （P<0.01）. As compared with model group， the fasting blood glucose and liver index of the mice in the metformin group and the ZJQP group decreased significantly （P<0.01）， the serum levels of TG and TC in the high-dose ZJQP group decreased significantly （P<0.05，P<0.01）， and the OGTT of mice in the metformin group and the high-dose ZJQP group improved （P<0.05）. In histopathology， as compared with the normal group， mice in the model group showed decreased lipid droplets and vacuoles in hepatocytes， and their volumes became larger. Compared with the model group， the ZJQP group and metformin group showed that the lipid droplets in liver tissues were reduced， the vacuoles in liver cells were reduced， and the volume was smaller. At the molecular level， as compared with the normal group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in liver tissues of mice in the model group were significantly up-regulated （P<0.01）. As compared with the model group， the mRNA and protein levels of FoxO1， PEPCK， G6Pase， and ApoC-Ⅲ in the ZJQP group was significantly decreased （P<0.01）. ConclusionZJQP can improve the glucose and lipid metabolism of T2DM with NAFLD and repair the pathological damage of liver， which may be through regulating the expression of FoxO1， PEPCK， G6Pase， ApoC-Ⅲ-related proteins in liver tissues to achieve the effects of regulating lipid， lowering glucose， and delaying hepatic steatosis.