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

doi:10.1016/j.bbrc.2009.04.136

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

Department of Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

136 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 language	English
Pages (from-to)	471-475
Number of pages	5
Journal	Biochemical and Biophysical Research Communications
Volume	384
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2009.04.136
Publication status	Published - 2009 Jul 10

Keywords

Diabetes
Nephropathy
Rapamycin
S6kinase
mTOR

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bbrc.2009.04.136

Cite this

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

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.",

keywords = "Diabetes, Nephropathy, Rapamycin, S6kinase, mTOR",

author = "Hiroyuki Mori and Ken Inoki and Kohsuke Masutani and Yu Wakabayashi and Kyoko Komai and Ryusuke Nakagawa and Guan, {Kun Liang} and Akihiko Yoshimura",

note = "Funding Information: We thank T. Yoshioka for her technical assistance. This study was supported by Grants-in-Aid for Scientific Research (S) and for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), and grants from the National Institutes of Health, USA (K.-L.G.).",

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AU - Mori, Hiroyuki

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AU - Komai, Kyoko

AU - Nakagawa, Ryusuke

AU - Guan, Kun Liang

AU - Yoshimura, Akihiko

N1 - Funding Information: We thank T. Yoshioka for her technical assistance. This study was supported by Grants-in-Aid for Scientific Research (S) and for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), and grants from the National Institutes of Health, USA (K.-L.G.).

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Y1 - 2009/7/10

N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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