Effect of saxagliptin on the expression of HIF-1α in the liver of diabetic rats with fatty liver

Abstract

The present study was designed to establish a rat model of type 2 diabetes mellitus (T2DM) complicated with fatty liver and to detect the expression of hypoxia-inducible factor-1α (HIF-1α) in liver tissue during the treatment with saxagliptin. Eighty male Wistar rats were randomly divided into two groups. One group was fed with high fat diet to establish T2DM model (n=40), and the other group was fed normally to serve as the control group (n=40). Successfully established rat T2DM models were randomly divided into two groups: The treatment group that received intraperitoneal injection of saxagliptin solution and the other the model group with normal breeding. Blood glucose, blood lipid, liver function and the expression of HIF-1α in liver tissue were detected. Levels of blood glucose in model treatment group were significantly higher than those in the control group (p<0.05).Levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in model and treatment group were significantly higher than those in control group (p<0.05), but were significantly reduced with the prolonged treatment (p<0.05). Levels of TC, TG, LDL-C, HDL-C, AST, ALT and GGT and expression level of HIF-1α were significantly higher in the model group than in control group before 3 weeks of treatment (p<0.05), but no significant differences were found after 3 weeks of treatment (p>0.05). Expression level of HIF-1α was decreased with the prolonged treatment, and no significant difference in expression level of HIF-1α was found 3 weeks after treatment (p>0.05). In conclusion, HIF-1α is highly expressed in rats with T2DM and fatty liver. Saxagliptin can effectively improve blood glucose, blood lipid and liver function and reduce the protein expression of HIF-1α in diabetic rats with fatty liver.