2032-P: The Effects of Liraglutide on Ameliorating Diabetic Kidney Disease Is via SIRT1/TXNIP Pathway

Abstract

GLP-1 receptor agonist is one of the most effective drugs to treat type 2 diabetes. LEADER Clinical Trials revealed that liraglutide exerted its renoprotective effect by reducing microalbumin-urine and slowing down the decline of eGFR. However, the underlying mechanism remains elusive. High glucose exposure upregulates the expression of TXNIP, a pro-oxidative stress and pro-apoptotic protein, by regulating histone acetylation. SIRT1, a deacetylase, also plays an important role in protecting renal function. We investigated the role of SIRT1/TXNIP pathway in the beneficial effect of liraglutide on improving renal function. In our study, eight-week old male C57BL/6 mice were subjected to a chow diet or a high fat diet (HFD) for 12 weeks. Then, mice were divided into groups as follows: NC, HFD, HFD+ Liraglutide (HL) group for 8 weeks. The results revealed that the body weight, fasting blood glucose, glucose tolerance and insulin sensitivity were statistically improved in HL group when compared with HFD group. Significant reduction of kidney lipid deposition and Bowman’s capsule space were observed in HL group based on the histology results. Besides, urine albumin-to-creatinine ratio and apoptosis in the kidney were ameliorated in the HL group. Western blotting results revealed the expression of genes involved in apoptosis was notably downregulated after liraglutide treatment. In addition, the protein expression of SIRT1 was upregulated, whereas TXNIP was downregulated in the HL group. Collectively, the data indicated that the effect of liraglutide on renoprotection is via SIRT1/TXNIP pathway. Disclosure R. Liang: None. M. Wang: None. C. Fu: None. F. Xu: None. M. Cai: None.