Gliquidone versus metformin: differential effects on aorta in streptozotocin induced diabetic rats
Authors: Tan Zhongju , Xu Zherong , Gui Qifeng , Wu Weizhen , Yang Yunmei 
Published: January 2024

Background
Diabetic cardiovascular complication is a major cause of mortality in type 2 diabetic patients. Hyperglycemia markedly increases the risk of cardiovascular disease. Endothelial dysfunction is common in type 2 diabetes mellitus (DM) and is an early indicator of diabetic vascular disease. Therefore, it is necessary to identify the effect of different hypoglycemic agents on vascular endothelium. The aim of the study was to examine and compare the effects of metformin and gliquidone on atherosclerotic lesions in streptozotocin-induced diabetic rats.

Methods
Forty male Sprague-Dawley rats (age, 8 weeks; weight, 180–200 g) were included in this study and fed with a normal chow diet for 1 week. Rats (n=10) served as the normal control group (NC group) were fed with a normal chow for another 2 weeks and received an injection of saline. The rest 30 rats fed with a high-fat diet for 2 weeks and injected streptozotocin were randomly assigned to three groups (n=10 rats per group) as follow: type 2 DM group (DM group), DM + gliquidone group (GLI group) and DM + metformin group (MET group). Five weeks later, all rats were fasted overnight and taken tail blood samples for biochemical determinations. Then rats in the NC and DM groups were administrated with normal saline, while rats in the MET and GLI groups were administrated with metformin (100 mg/kg) or gliquidone (10 mg/kg), respectively. All medicines were given via intragastric administration for 8 weeks. After 16 weeks, plasma triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) were measured. The aortic arch was isolated from diabetic rats and was assessed by pathological sectioning using H&E staining.

Results
Metformin treatment prevented weight gain ((315.80±52.16) g vs. (318.70±68.48) g, P=0.773), improved plasma TG, HDL-C and LDL-C levels (P=0.006, 0.003, 0.001, respectively, all P <0.05). However, gliquidone showed no significant effects on plasma TG and TC levels (P=0.819, 0.053, respectively). LDL-C and HDL-C in the GLI group changed ((0.46±0.10) mmol/L vs. (0.36±0.14) mmol/L, P=0.007; (0.99±0.27) mmol/L vs. (1.11±0.18) mmol/L, P=0.049). Both metformin and gliquidone treatment lowered blood glucose levels (P=0.001, 0.004, respectively, P <0.05). Under light microscopy, no changes were observed in the aortic wall structure of each layer; the intima was smooth and the membrane elastic fibers were normal in the NC group. In the DM group, the aortic wall structure was unclear, the intima was thickened with irregular intima, and membrane elastic fibers collapsed. The aortic intima in the MET and GLI groups was smoother compared with the DM group, but the endothelial structure of the MET group was closer to that of the NC group.

Conclusions
Both metformin and gliquidone have anti-atherosclerotic effects. But the endothelial structure of the MET group was closer to that of the NC group. Metformin and gliquidone therapy can reduce serum level of LDL-C and increase level of HDL-C, whereas gliquidone therapy did not lose weight and decrease serum level of TG. These data may have important implications for the treatment of patients with type 2 DM.