論文

査読有り
2016年8月1日

Inhibition of SGLT2 alleviates diabetic nephropathy by suppressing high glucose-induced oxidative stress in type 1 diabetic mice

Pharmacology Research and Perspectives
  • Takashi Hatanaka
  • ,
  • Daisuke Ogawa
  • ,
  • Hiromi Tachibana
  • ,
  • Jun Eguchi
  • ,
  • Tatsuyuki Inoue
  • ,
  • Hiroshi Yamada
  • ,
  • Kohji Takei
  • ,
  • Hirofumi Makino
  • ,
  • Jun Wada

4
4
開始ページ
e00239
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/prp2.239
出版者・発行元
Wiley-Blackwell Publishing Ltd

It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured. Expansion of the mesangial matrix, interstitial fibrosis, and macrophage infiltration in kidneys were evaluated by histology. Oxidative stress and apoptosis were evaluated in kidneys and cultured proximal tubular epithelial cells. Compared with nontreated mice, dapagliflozin and insulin decreased blood glucose and hemoglobin A1c levels equally. Urine volume and water intake increased significantly in the dapagliflozin-treated group compared with those in the insulin-treated group, but there were no differences in body weight or blood pressure between the two groups. Macrophage infiltration and fibrosis in renal interstitium improved significantly in the dapagliflozin group compared with the insulin group. Oxidative stress was attenuated by dapagliflozin, and suppression occurred in a dose-dependent manner. RNAi knockdown of SGLT2 resulted in reduced oxidative stress. Dapagliflozin ameliorates diabetic nephropathy by suppressing hyperglycemia-induced oxidative stress in a manner independent of hyperglycemia improvement in Akita mice. Our findings suggest that dapagliflozin may be a novel therapeutic approach for the treatment of diabetic nephropathy.

リンク情報
DOI
https://doi.org/10.1002/prp2.239
URL
https://www.ncbi.nlm.nih.gov/pubmed/28116093
URL
http://orcid.org/0000-0003-1468-5170
ID情報
  • DOI : 10.1002/prp2.239
  • ISSN : 2052-1707
  • ORCIDのPut Code : 43365880
  • SCOPUS ID : 85019870969

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