研究者情報

ヤマダ　ショウヘイ   YAMADA SHOHEI   山田将平    所属   医学部医学科 腎臓・高血圧内科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Renoprotective effect of GLP-1 receptor agonist, liraglutide,in early-phase diabetic kidney disease in spontaneously diabetic torii fatty rats.
掲載誌名	正式名：Clinical and Experimental Nephrology 略　 称：Clin Exp Nephrol
掲載区分	国外
出版社名	Springer
巻・号・頁	25,365-375頁
著者・共著者	Yamada S, Tanabe J, Ogura Y, Nagai Y, Sugaya T, Ohata K, Natsuki Y, Ichikawa D, Watanabe S, Inoue K, Hoshino S, Kimura K, Shibagaki Y, Kamijo-Ikemori A
担当区分	筆頭著者
発行年月	2021/04
概要	Background The aim of this study is to investigate the renoprotective effect of the GLP-1 receptor agonist, liraglutide, in early-phase diabetic kidney disease (DKD) using an animal model of type 2 diabetes with several metabolic disorders. Methods Male 8-week-old spontaneously diabetic Torii (SDT) fatty rats (n = 19) were randomly assigned to three groups. The liraglutide group (n = 6) was injected subcutaneously with liraglutide. Another treatment group (n = 6) received subcutaneous insulin against hyperglycemia and hydralazine against hypertension for matching blood glucose levels and blood pressure with the liraglutide group. The control groups of SDT fatty (n = 7) and non-diabetic Sprague-Dawley rats (n = 7) were injected only with a vehicle. Results The control group of SDT fatty rats exhibited hyperglycemia, obesity, hypertension, hyperlipidemia, glomerular sclerosis, and tubulointerstitial injury with high urinary albumin and L-FABP levels. Liraglutide treatment reduced body weight, food intake, blood glucose and blood pressure levels, as well as ameliorated renal pathologic findings with lower urinary albumin and L-FABP levels. Liraglutide increased expressions of phosphorylated (p)-eNOS and p-AMPK in glomeruli, downregulated renal expression of p-mTOR, and increased renal expressions of LC3B-II, suggesting activation of autophagy. However, these effects were not caused by the treatments with insulin and hydralazine, despite comparable levels of hyperglycemia and hypertension to those achieved with liraglutide treatment. Conclusions Liraglutide may exert a renoprotective effect via prevention of glomerular endothelial abnormality and preservation of autophagy in early-phase DKD, independently of blood glucose, and blood pressure levels.