Protective effects of liraglutide on renal tissues and related mechanism in diabetic rats

Abstract

Objective To explore the effects of glucagon-like peptide-1 (GLP-1) analogues liraglutide on renal tissues of diabetic rats and its mechanism. Methods Forty male SD rats were randomly divided into four groups: normal control rats (NC group), normal control rats with liraglutide treatment (NCL group), diabetic rats (DM group) and diabetic rats with liraglutide treatment. The body weight, glycosylated hemoglobin (HbA1c), albuminuria/creatinine (A/C), kidney index (KI, kidney mass/body mass) were detected after 8 weeks treatment. The gene expression of tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6), interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1), type IV collagen, and transforming growth factor-β1 (TGF-β1) were measured by real time PCR. The protein expression of COL-Ⅳ, NF-κB, GLP-1R and phosphorylation levels of ERK, JNK and p38MAPK were evaluated by Western blotting. Results Compared to NC group, the body weight in DM group was reduced, and HbA1c, KI, A/C levels were significantly increased (P<0.05). The gene expression of TNF-α, IL-6, IL-1β, MCP-1, TGF-β1 and COL-IV was increased (P<0.05). Moreover, the protein expression of NF-κB in the nucleus of the kidney tissues and the phosphorylation levels of ERK, JNK and p38MAPK were significantly increased in DM group, accompanied by the decline of GLP-1R protein level (P<0.05). After 8 weeks of liraglutide treatment, the urinary protein excretion was reduced, and the gene expressions of TNF-α, IL-6, IL-1β, MCP-1, TGF-β1, COL-IV were inhibited. Importantly, the phosphorylation levels of ERK and JNK were significantly inhibited and the expression of NF-κB protein in the nucleus of the kidney tissue was reduced (P<0.05). These changes may be associated with the increased expression of GLP-1R after liraglutide treatment. However, blood glucose and the body weight in DML group rats had no significant changes after liraglutide treatment. Conclusion Liraglutide has a protective effect on renal tissues through inhibiting ERK and JNK phosphorylation and related inflammation in diabetic rats. Key words: Diabetic nephropathies; Inflammation; Glucagon-like peptide 1; Liraglutide