Nonalcoholic fatty liver disease and cirrhosis are strongly associated with insulin resistance and glucose intolerance. To date, the influence of metformin on glycogen synthesis in the liver is controversial. Limited studies have evaluated the effect of metformin on hepatic insulin signaling pathway in vivo. In this study, an insulin-resistant rat model of nonalcoholic steatohepatitis and cirrhosis was developed by high-fat and high-sucrose diet feeding in combination with subcutaneous injection of carbon tetrachloride. Liver tissues of the model rats were featured with severe steatosis and cirrhosis, accompanied by impaired liver function and antioxidant capacity. The glucose tolerance was impaired, and the index of insulin resistance was increased significantly compared with the control. The content of hepatic glycogen was dramatically decreased. The expression of insulin receptor β (IRβ); phosphorylations of IRβ, insulin receptor substrate 2 (IRS2), and Akt; and activities of phosphatidylinositol 3-kinase (PI3K) and glycogen synthase (GS) in the liver were significantly decreased, whereas the activities of glycogen synthase kinase 3α (GSK3α) and glycogen phosphorylase a (GPa) were increased. Metformin treatment remarkably improved liver function, alleviated lipid peroxidation and histological damages of the liver, and ameliorated glucose intolerance and insulin resistance. Metfromin also significantly upregulated the expression of IRβ; increased the phosphorylations of IRβ, IRS2, and Akt; increased the activities of PI3K and GS; and decreased GSK3α and GPa activities. In conclusion, our study suggests that metformin upregulates IRβ expression and the downstream IRS2/PI3K/Akt signaling transduction, therefore, to increase hepatic glycogen storage and improve insulin resistance. These actions may be attributed to the improved liver histological alterations by metformin.
To explore the application value of tumor markers carcinoembryonic antigen and cytokeratin 19 fragment in the progression and prognosis of middle-advanced non-small cell lung cancer. Clinical data of 97 patients initially diagnosed with lung lesions in our hospital from January 2018 to December 2019 were collected and divided into the lung cancer group and benign lesion group. There were 52 patients diagnosed with stage I or II lung cancer by computed tomography and clinical diagnosis in the lung cancer group and 45 patients with benign lesions in the benign lesion group. The levels of serum tumor markers were detected by electrochemiluminescence immunoassay. The results showed that the levels of carcinoembryonic antigen and cytokeratin 19 were significantly higher in the lung cancer group compared with the benign lesion group and the difference was statistically significant (p<0.05). Both carcinoembryonic antigen and cytokeratin 19 can be used in the diagnosis of squamous cell carcinoma and adenocarcinoma. The sensitivity of the combined detection was significantly higher than that of the single detection, while the specificity of the combined detection was significantly lower than that of carcinoembryonic antigen alone (p<0.05). In lung cancer with positive combined detection, the proportion of adenocarcinoma was significantly higher than that of squamous cell carcinoma. When cytokeratin 19 was positive and carcinoembryonic antigen was negative, the proportion of squamous cell carcinoma was significantly higher than that of adenocarcinoma. Serum carcinoembryonic antigen and cytokeratin 19 were abnormally highly expressed in non-Small cell lung cancer patients, which are useful for clinical diagnosing, treatment planning, efficacy monitoring, and prognosis evaluation.
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