Effect of metformin on the insulin resistance in a rat model of type 2 diabetes mellitus / 中国组织工程研究

ABSTRACT

BACKGROUND:More than 10 kinds of lipid metabolism-related genes have been found, and endocrine dysfunction mediated by these genes is an important pathological basis for the occurrence and development of insulin resistance. OBJECTIVE:To investigate the effects of metformin on serum lipid profiles and the expression levels of various genes associated with insulin resistance, as well as the histopathological changes of the liver and pancreas in rats with type 2 diabetes melitus. METHODS:A type 2 diabetes mellitus rat model was established by feeding a high-fat diet to the rats for 4 weeks, combined with the intraperitoneal injection of streptozotocin (35 mg/kg). In the meanwhile, metformin was administered orally (400 mg/kg?d) (model group) or nothing (control group). Semi-quantitative RT-PCR, histopathological and biochemical examinations were then performed. RESULTS AND CONCLUSION:Metformin improved the symptoms of insulin resistance by normalizing the serum lipid profiles in the diabetic rats. Furthermore, metformin upregulated the expression levels of insulin receptors and genes associated with lipid metabolism, including acyl-CoA oxidase, carnitine palmitoyl transferase-1 and peroxisome proliferator activated receptor-α. In addition, metformin downregulated the expression levels of fetuin-A and retinol binding protein-4, and improved the expression of perilipin that had been reduced in the type 2 diabetes mellitus rats. Metformin was shown to induce positive signaling for insulin and the regeneration of pancreaticβcells in the pancreas. These results suggest that metformin ameliorates the insulin resistance induced by type 2 diabetes mellitus via regulating the expression levels of fetuin-A, retinol binding protein-4, perilipin and various genes associated with lipid metabolism.