論文

査読有り 国際誌
2020年6月5日

Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice.

International journal of molecular sciences
  • Kazuhiko Fukushima
  • ,
  • Shinji Kitamura
  • ,
  • Kenji Tsuji
  • ,
  • Yizhen Sang
  • ,
  • Jun Wada

21
11
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms21114054

Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i-HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.

リンク情報
DOI
https://doi.org/10.3390/ijms21114054
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32517059
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312919
ID情報
  • DOI : 10.3390/ijms21114054
  • PubMed ID : 32517059
  • PubMed Central 記事ID : PMC7312919

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