Abstract【Objective】To explore the mechanism of metformin in the treatment of obese type 2 diabetes (T2DM) rats. 【Methods】Adult male Wistar rats (90 rats) were fed with high glucose and high fat, and then injected with streptozotocin intraperitoneally to establish diabetes obesity model. They were randomly divided into control group, model group and experimental group. The rats in the model group and the experimental group were fed with high-fat and high sugar diet for 21 days, supplemented with 55 mg / kg intraperitoneal injection of streptozotocin (STZ) to induce T2DM model, while the rats in the control group were fed with ordinary diet as normal control. The rats in the control group and the model group were given the same amount of normal saline by gavage once a day. After 16 weeks of continuous gavage, the rats were killed. The urine urea nitrogen (UUN), urine creatinine (UCr) and 24-hour urine protein content (24hPro) were measured. Serum cholesterol (TC), free fatty acid (FFA), triglyceride (TG), fasting blood glucose (FPG), fasting insulin (FINS), insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were measured. HE method was used to detect renal pathological changes;The expression of FoxO 1, Wnt-1 and β-Catenin in serum, pancreas and liver of rats was measured by Western blot. 【Results】Compared with the control group, the 24hPro, UCr, UUN, TC, FFA, TG, FPG, FINS, ISI, HOMA-IR contents of the model group and the experimental group were significantly increased; compared with the model group, the above biochemical indexes contents of the experimental group were significantly reduced, and the differences were statistically significant (P<0.05). In the control group, there was no obvious abnormality in renal tissue morphology, and the cell structure was basically normal. In the model group, a large number of vacuolar degeneration, deformation, abscission and partial necrosis were found in the renal tubular epithelial cells, and the renal tubules were dilated, fibrotic or atrophic, dilated and sparsely arranged. In the experimental group, the symptoms were improved obviously, the cell edema and vacuole were reduced, and the damage and destruction of renal tubule structure were improved. Compared with the control group, the expression of FoxO1, Wnt-1 and β- Catenin protein in serum, pancreas, liver and kidney of rats in the model group and the experimental group was significantly increased; compared with the model group, the expression of FoxO1, Wnt-1 and β- Catenin protein in the experimental group was significantly decreased, and the difference was statistically significant (P<0.05). 【Conclusion】Metformin has renal protective effect on T2DM obese rats. It can inhibit the injury of T2DM obese rats by regulating FoxO1 / Wnt /β- Catenin signal pathway.
SHAN Xin-ping,SONG Li-ying,LI Ling. Study on the Mechanism of Metformin in the Treatment of Obese T2DM Rats[J]. JOURNAL OF CLINICAL RESEARCH, 2019, 36(12): 2329-2332.
2019, Vol. 36 
