The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential

Hiroyuki Mori, Ken Inoki, Kohsuke Masutani, Yu Wakabayashi, Kyoko Komai, Ryusuke Nakagawa, Kun Liang Guan, Akihiko Yoshimura

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Diabetic nephropathy (DN) associated with type 2 diabetes is the most common cause of end-stage renal disease (ESRD) and a serious health issue in the world. Currently, molecular basis for DN has not been established and only limited clinical treatments are effective in abating the progression to ESRD associated with DN. Here we found that diabetic db/db mice which lack the leptin receptor signaling can be used as a model of ESRD associated with DN. We demonstrated that p70S6-kinase was highly activated in mesangial cells in diabetic obese db/db mice. Furthermore, systemic administration of rapamycin, a specific and potent inhibitor of mTOR, markedly ameliorated pathological changes and renal dysfunctions. Moreover, rapamycin treatment shows a significant reduction in fat deposits and attenuates hyperinsulinemia with few side effects. These results indicate that mTOR activation plays a pivotal role in the development of ESRD and that rapamycin could be an effective therapeutic agent for DN.

Original languageEnglish
Pages (from-to)471-475
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume384
Issue number4
DOIs
Publication statusPublished - 2009 Jul 10

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Keywords

  • Diabetes
  • Nephropathy
  • Rapamycin
  • S6kinase
  • mTOR

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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