Objective To explore the expression differences of the docking protein 1(DOK1)gene in multiple tissues of mice during the development stage from prediabetes to type 2 diabetes mellitus(T2DM),as well as its correlation with blood lipid levels.Methods The mice were divided into the 0 d group(control),the 20 d group,the 40 d group,the 60 d group,the 80 d group and the T2DM group.The 0 d group was fed with normal diet,while the other four groups were fed with high-fat diet to establish the prediabetes model.On this basis,the T2DM group was given low-dose multiple intraperitoneal injections of streptozotocin(STZ)to establish the T2DM model.The fasting and intraperitoneal glucose tolerance test(IPGTT)and insulin tol-erance test(IPITT)blood glucose of mice in each group were detected,and the expression of the DOK1 gene in nine tissues(heart,liver,kidney,skeletal muscle,pancreas,adipose,spleen,lung and colon tissues)was de-tected by qPCR.The level of DOK1 in serum was determined by ELISA,and the lipid level in serum was measured by an automatic biochemical analyzer.The correlations between serum DOK1 and TG,TC,HDL-C,LDL-C,lipoprotein A[LP(a)],and free fatty acids(FFA)were analyzed by Spearman correlation analysis.Re-sults The prediabetic and T2DM model mice were successfully established.Compared with the 0 d group,the blood glucose and lipid levels in the 80 d group and the T2DM group were significantly increased(P<0.001).Compared with the 0 d group,the expression level of DOK1 mRNA in the T2DM group was significantly de-creased in heart,liver,kidney,skeletal muscle,pancreas and adipose tissue(P<0.05).Compared with the 0 d group,the expression level of DOK1 mRNA in the 80 d group was significantly decreased in heart,liver,kid-ney and skeletal muscle tissue(P<0.05).Compared with the 0 d group,the expression levels of DOK1 mR-NA in the 40 d group and the 60 d group was significantly decreased in the liver tissues(P<0.05).Compared with group 0 d,there was no statistically significant difference in the expression level of DOK1 mRNA in the spleen,lung and colon tissues among each group(P>0.05).DOK1 in the 80 d group and the T2DM group was negatively correlated with TG,TC,LDL-C,LP(a),and FFA(r=-0.787 8,-0.727 2,-0.763 7,-0.764 2,-0.892 5,P<0.001),while positively correlated with HDL-C(r=0.961 3,P<0.001).Conclu-sion The reduction of DOK is related to the mechanism of insulin resistance and may play a key role in lipid metabolism disorders associated with diabetes.

Interferon-stimulating gene 15(ISG15),an ubiquitin-like molecule belonging to the superfamily of ubiquitin-like proteins,is highly expressed in various malignant tumors and induced by type Ⅰ interferon.How-ever,its specific regulatory mechanism remains unclear.Numerous studies have demonstrated its close association with tumorigenesis and development.In this study,we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma,esophageal carcinoma,gastric carcinoma,colorectal carcinoma,and other cancers.Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.

Interferon-stimulating gene 15(ISG15),an ubiquitin-like molecule belonging to the superfamily of ubiquitin-like proteins,is highly expressed in various malignant tumors and induced by type Ⅰ interferon.How-ever,its specific regulatory mechanism remains unclear.Numerous studies have demonstrated its close association with tumorigenesis and development.In this study,we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma,esophageal carcinoma,gastric carcinoma,colorectal carcinoma,and other cancers.Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.