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Abstract: PO0913

Renoprotective Effect of a GLP-1 Receptor Agonist, Liraglutide, in an Early Phase of Diabetic Kidney Disease in Spontaneously Diabetic Tori Fatty Rats

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Yamada, Shohei, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Tanabe, Jun, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Sugaya, Takeshi, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Ichikawa, Daisuke, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Kimura, Kenjiro, JCHO Tokyo Takanawa Hospital, Shinagawa, Tokyo, Japan
  • Shibagaki, Yugo, Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
  • Ikemori, Atsuko, Department of Anatomy, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
Background

Early intervention is extremely needed for preventing the progression of diabetic kidney disease (DKD) to end stage renal disease. The aim of this study is to investigate the renoprotective effect of GLP-1 receptor agonist, liraglutide, in early phase of DKD and to determine the mechanisms underlying its effects using an animal model of type 2 diabetes with various metabolic disorders.

Methods

Male spontaneously diabetic torii (SDT) fatty rats (n = 30) at 8 weeks of age were randomly assigned to three groups; the liraglutidegroup (n = 11) was subcutaneous injected liraglutide. Another treatment group(n = 6) was subcutaneous administered insulin against hyperglycemia and was given hydralazine against hypertension for matching both levels of blood glucose and blood pressure with the liraglutidegroup. A control group (n = 13) was injected only a vehicle. Urinary tubular marker, L-type fatty acid-binding protein (L-FABP), was measured to evaluate the effect of liraglutide against tubulointerstitial damage.

Results

Control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, glomerular sclerosis and tubulointerstitial injury with high levels of urinary albumin and L-FABP, whereas treatment with liraglutide reduced body weight, food intake, both blood glucose and blood pressure levels, as well as, amelioration of renal pathological findings with lower levels of both urinary albumin and L-FABP. Liraglutide increased in expressions of both phosphorylated (p)-eNOS and p-AMPK in glomeruli. It also down-regulated renal expression of p-mTOR, and up-regulated renal expressions of LC-3 II, suggesting activation of autophagy. However, these effects were not brought by the treatments of both insulin and hydralazine, despite comparable levels of both hyperglycemia and hypertension to those of liraglutide.

Conclusion

Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial dysfunction and acceleration of autophagy in the early phase of DKD, independently of both blood glucose and blood pressure levels. Furthermore, urinary L-FABP may be a useful marker reflecting the therapeutic efficacy of liraglutide.