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CJAP ›› 2020, Vol. 36 ›› Issue (6): 565-570.doi: 10.12047/j.cjap.6001.2020.119

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Effect of dapagliflozin on gene expression of glucose transporter 2 and glucose transporter 4 in kidney of type 2 diabetic rats

XU Yun1, CHEN Xue-hui1, BAI Li-wei1, YIN Qing-feng1, FENG Chun-yu2 , ZHANG Qing-gui1△   

  1. 1. The Department ofEndocrinology, Ward 1, the First Affiliated Hospital of Xinxiang Medical University, Weihui 453100;
    2. Internal Medicine,Ward 3, the People's Hospital of Wei Hui, Weihui 453100, China
  • Received:2020-02-24 Revised:2020-11-12 Online:2020-11-28 Published:2021-03-15

Abstract: Objective: To investigate the effects of dapagliflozin on the gene expressions of glucose transporter 2 (GLUT2) and glucose transporter 4 (GLUT4) in type 2 diabetic rats. Methods: High fat diet and 40 mg/kg streptozotocin (STZ) were used to establish the rat model of type 2 diabetes mellitus. When the fasting blood glucose (FBG) content was more than or equal to 16.7 mmol/L, the model was established successfully. After successful modeling, the rats were randomly divided into model group (group B, normal saline), dapagliflozin low-dose group (Group C, 0.75 mg/kg), dapagliflozin middle dose group (Group D, 1.5 mg/kg) and dapagliflozin high-dose group (Group E, 3.0 mg/kg), with 6 rats in each group. Six healthy SD rats were selected as normal control group (group A, normal saline). Each group was administrated by gavage once a day for 7 weeks. The body weight, serum FBG, hemoglobin A1c (HbA1c), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured after 7 weeks. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in serum and kidney were measured by enzyme-linked immunosorbent assay (ELISA). HE staining was used to observe the pathological changes of kidney. The protein expressions of GLUT2 and GLUT4 were detected by Western blot. RT-qPCR was used to detect the relative expressions of GLUT2 and GLUT4 mRNA in kidney tissue. Results: Compared with group A, the body weight, SOD, GSH-Px levels of rats in each group were significantly decreased (P<0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly increased (P<0.05), renal pathological damage was serious, the relative expressions of GLUT2, GLUT4 mRNA and protein in renal tissue were significantly decreased (P<0.05). Compared with group B, the body weight, SOD, GSH-Px levels and the mRNA relative expressions of GLUT2 and GLUT4 in group C, group D and group E were significantly increased (P<0.05), while the levels of FBG, HbA1c, BUN, SCR and MDA were significantly decreased (P<0.05). The renal pathological damage in group D and group E was significantly alleviated, and the expressions of GLUT2 and GLUT4 protein in renal tissue were significantly increased (all P<0.05). Conclusion: Dapagliflozin can alleviate the condition of type 2 diabetic rats and up regulate the expression of GLUT2 and GLUT4 genes in kidney.

Key words: dapagliflozin, type 2 diabetes mellitus, rats, GLUT2, GLUT4

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