ß-catenin mediates the effect of GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose diet.

The hypoglycemic drug GLP-1 receptor agonist can ameliorate hepatic steatosis but the mechanism is not clear. Intake of high fructose leads to non-alcoholic fatty liver disease by stimulating lipid synthesis, and ß-catenin is the key molecule for realizing GLP-1 function in extrahepatic tissues; with the discovery of GLP-1 receptor in liver, we speculate that ß-catenin might mediate GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose. Wistar rats were fed with high fructose diet for 8 weeks and then treated with GLP-1 receptor agonist exenatide for 4 weeks; the changes of lipid synthesis pathway factors, the expression and nuclear translocation of ß-catenin, and the hepatic steatosis of the rats were observed. After the intervention of exenatide, the hepatic steatosis induced by high fructose was improved, the nuclear translocation and expression of ß-catenin were facilitated, and the mRNA and protein expression of the upstream regulator SREBP-1 and the downstream key enzymes ACC, FAS and SCD-1 of de novo lipogenesis were down-regulated. GLP-1 receptor agonist may ameliorate hepatic steatosis induced by high fructose by ß-catenin regulating de novo lipogenesis pathway. GLP-1 receptor agonist may be a potential new drug for the treatment of non-alcoholic fatty liver disease, and the ß-catenin may be an important target for the drug therapy.

[A study on endothelial function and inflammation factors in the first degree relatives of type 2 diabetics with normal glucose tolerance].

OBJECTIVE: To study the vascular endothelial function and the level of inflammation factors in the first degree relatives (FDR) of type 2 diabetes (T2DM) patients with normal glucose tolerance and related factors. METHODS: Vascular endothelial function, plasma plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1) and insulin active index (IAI) were measured in 57 FDR and 31 controls. RESULTS: As compared with the controls, there were less endothelium-dependent vasodilation [(12.45 +/- 3.37)% vs (5.03 +/- 0.34)%] and IAI [(-3.79 +/- 0.57) vs (-4.11 +/- 0.46)], higher PAI-1 [(30.46 +/- 12.28) microg/L vs (39.25 +/- 6.54) microg/L] and higher VCAM-1 [(637.31 +/- 107.32) microg/L vs (742.39 +/- 124.31) microg/L] in the FDR (P < 0.05). CONCLUSION: There were decreased IAI, damaged endothelial function and impaired fibrinolysis in the first degree relatives of T2DM patients with normal glucose tolerance.