C1q tumor necrosis factor-related proteins (CTRPs), which are members of the adipokine superfamily, have gained significant interest in the recent years. CTRPs are homologs of adiponectin with numerous functions and are closely associated with metabolic diseases, such as abnormal glucose and lipid metabolism and diabetes. Previous studies have demonstrated that CTRPs are highly involved in the regulation of numerous physiological and pathological processes, including glycolipid metabolism, protein kinase pathways, cell proliferation, cell apoptosis and inflammation. CTRPs also play important roles in the development and progression of numerous types of tumor, including liver, colon and lung cancers. This observation can be attributed to the fact that diabetes, obesity and insulin resistance are independent risk factors for tumorigenesis. Numerous CTRPs, including CTRP3, CTRP4, CTRP6 and CTRP8, have been reported to be associated with tumor progression by activating multiple signal pathways. CTRPs could therefore be considered as diagnostic markers and therapeutic targets in some cancers. However, the underlying mechanisms of CTRPs in tumorigenesis remain unknown. The present review aimed to determine the roles and underlying mechanisms of CTRPs in tumorigenesis, which may help the development of novel cancer treatments in the future.

Background Coronary heart disease (CHD) is one of the most common causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Oxidative stress is one of the important contributors to the pathogenesis of CHD. Sestrin2 is a stress-induced antioxidant protein that plays a important role in T2DM and CHD. However, the relationship between serum Sestrin2 levels and T2DM with CHD remains unclear. Aim This study aimed to investigate the relationship between serum Sestrin2 levels and CHD in patients with type 2 diabetes. Methods A total of 70 T2DM patients with CHD and 69 T2DM patients were enrolled in this study. Clinical features and metabolic indices were identified. Serum Sestrin2 was measured by ELISA. Results Serum Sestrin2 levels in T2DM-CHD groups were significantly lower compared with the T2DM group (11.17 (9.79, 13.14) ng/mL vs 9.46 (8.34, 10.91) ng/mL). Bivariate correlation analysis revealed that serum Sestrin2 levels were negatively correlated with age (r = − 0.256, P = 0.002), BMI (r = − 0.206, P = 0.015), FBG (r = − 0.261, P = 0.002) and Tyg index (r = − 0.207, P < 0.014). Binary logistic regression suggested that low serum Sestrin2 levels were related to the increased risk of T2DM-CHD (P < 0.05). In addition, the receiver operating characteristic analysis revealed that the area under the curve of Sestrin2 was 0.724 (95% CI 0.641–0.808, P < 0.001) to predict T2DM-CHD patients (P < 0.001). Conclusion The Sestrin2 levels were highly associated with CHD in diabetes patients. Serum Sestrin2 may be involved in the occurrence and development of diabetic with CHD.

Object. L6 cells were cultured to explore the possible mechanism underlying the improvement of insulin resistance by Liraglutide (LR). Methods. Cells were divided into 5 groups—control, high-fat, 10 nmol/L LR + 0.6  mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6  mmol/L PA (100LR), and 1000 nmol/L LR + 0.6  mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed. Results. We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group ( P < 0.01 ). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. 8.15 ± 0.35 ); ( 1.00 ± 0.04 vs. 2.46 ± 0.08 ); ( 2.88 ± 0.55 vs. 8.29 ± 0.52 ), P < 0.01 ) and protein (( 3338.13 ± 333.15 vs. 4963.98 ± 277.29 ); ( 1978.85 ± 124.24 vs. 2676.07 ± 100.64 ); ( 3372.00 ± 219.84 vs. 6083.20 ± 284.70 ), both P < 0.01 ) expression decreased in the LR group. The expression levels of GLUT4 mRNA (( 0.75 ± 0.04 vs. 0.34 ± 0.03 ), P < 0.01 ) and protein (( 3443.71 ± 191.89 vs. 2137.79 ± 118.75 ), P < 0.01 ) increased. Conclusion. Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors.

In this study, we aimed to determine whether liraglutide could effectively reduce insulin resistance (IR) by regulating Sestrin2 (SESN2) expression in L6 rat skeletal muscle cells by examining its interactions with SESN2, autophagy, and IR. L6 cells were incubated with liraglutide (10–1000 nM) in the presence of palmitate (PA; 0.6 mM), and cell viability was detected using the cell counting kit-8 (CCK-8) assay. IR-related and autophagy-related proteins were detected using western blotting, and IR and autophagy-related genes were analyzed using quantitative real-time polymerase chain reaction. Silencing SESN2 was used to inhibit the activities of SESN2. A reduction in insulin-stimulated glucose uptake was observed in PA-treated L6 cells, confirming IR. Meanwhile, PA decreased the levels of GLUT4 and phosphorylation of Akt and affected SESN2 expression. Further investigation revealed that autophagic activity decreased following PA treatment, but that liraglutide reversed this PA-induced reduction in autophagic activity. Additionally, silencing SESN2 inhibited the ability of liraglutide to up-regulate the expression of IR-related proteins and activate autophagy signals. In summary, the data showed that liraglutide improved PA-induced IR in L6 myotubes by increasing autophagy mediated by SESN2.

Tumors of the digestive system have always received attention, and their occurrence and development are regulated by various mechanisms such as inflammation and immunity, glucose and lipid metabolism, and tumor angiogenesis. Complement Clq/TNF-related protein 6 (CTRP6) is a member of the CTRP family; it is widely expressed in various tissues and cell types, and plays a biological role in a number of mechanisms, such as glucose and lipid metabolism and inflammation. Recent studies have revealed the tumor-promoting effect of CTRP6 in gastric cancer, liver cancer, colorectal cancer and other gastrointestinal tumors, but, to the best of our knowledge, there has been no systematic discussion on the tumor-promoting mechanism of CTRP6. The present study reviews the role of CTRP6 in tumors of the digestive system and its possible mechanisms.