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

109 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

Fingerprint

Diabetic Nephropathies
Sirolimus
Chronic Kidney Failure
Leptin Receptors
Therapeutics
Medical problems
Mesangial Cells
Hyperinsulinism
Phosphotransferases
Deposits
Chemical activation
Fats
Type 2 Diabetes Mellitus
Health
Kidney

Keywords

  • Diabetes
  • mTOR
  • Nephropathy
  • Rapamycin
  • S6kinase

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential. / Mori, Hiroyuki; Inoki, Ken; Masutani, Kohsuke; Wakabayashi, Yu; Komai, Kyoko; Nakagawa, Ryusuke; Guan, Kun Liang; Yoshimura, Akihiko.

In: Biochemical and Biophysical Research Communications, Vol. 384, No. 4, 10.07.2009, p. 471-475.

Research output: Contribution to journalArticle

Mori, Hiroyuki ; Inoki, Ken ; Masutani, Kohsuke ; Wakabayashi, Yu ; Komai, Kyoko ; Nakagawa, Ryusuke ; Guan, Kun Liang ; Yoshimura, Akihiko. / The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 384, No. 4. pp. 471-475.
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AU - Nakagawa, Ryusuke

AU - Guan, Kun Liang

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