Role of Rho-kinase in regulation of insulin action and glucose homeostasis

Noboru Furukawa; Pat Ongusaha; Wan Jin Jahng; Kazushi Araki; Cheol Soo Choi; Hyo Jeong Kim; Yong Hee Lee; Kozo Kaibuchi; Barbara B. Kahn; Hiroaki Masuzaki; Jason K. Kim; Sam W. Lee; Young Bum Kim

doi:10.1016/j.cmet.2005.06.011

Role of Rho-kinase in regulation of insulin action and glucose homeostasis

Noboru Furukawa, Pat Ongusaha, Wan Jin Jahng, Kazushi Araki, Cheol Soo Choi, Hyo Jeong Kim, Yong Hee Lee, Kozo Kaibuchi, Barbara B. Kahn, Hiroaki Masuzaki, Jason K. Kim, Sam W. Lee, Young Bum Kim

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

134 Citations (Scopus)

Abstract

Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we show that insulin stimulation of glucose transport is impaired when ROK is chemically or biologically inhibited in cultured adipocytes and myotubes and in isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition of ROK activity in mice causes insulin resistance by reducing insulin-stimulated glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. These results strongly suggest that ROK regulates insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an important regulator of insulin signaling and glucose metabolism.

Original language	English
Pages (from-to)	119-129
Number of pages	11
Journal	Cell Metabolism
Volume	2
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2005.06.011
Publication status	Published - 08-2005
Externally published	Yes

All Science Journal Classification (ASJC) codes

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2005.06.011

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@article{80f1dc3c02f846dfa557658e29ba38fb,

title = "Role of Rho-kinase in regulation of insulin action and glucose homeostasis",

abstract = "Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we show that insulin stimulation of glucose transport is impaired when ROK is chemically or biologically inhibited in cultured adipocytes and myotubes and in isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition of ROK activity in mice causes insulin resistance by reducing insulin-stimulated glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. These results strongly suggest that ROK regulates insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an important regulator of insulin signaling and glucose metabolism.",

author = "Noboru Furukawa and Pat Ongusaha and Jahng, {Wan Jin} and Kazushi Araki and Choi, {Cheol Soo} and Kim, {Hyo Jeong} and Lee, {Yong Hee} and Kozo Kaibuchi and Kahn, {Barbara B.} and Hiroaki Masuzaki and Kim, {Jason K.} and Lee, {Sam W.} and Kim, {Young Bum}",

note = "Funding Information: We would like to thank Yasuhiko Minokoshi, Michael Greene, Matthew Brady, and Jean Chan for comments on the manuscript; Jang Youn, Nimesh Mody, Qin Yang, Christian Bjorbaek, Takamasa Higashimori, Mustuki Amano, and Erin Kerstin for technical help; Amira Klip for L6 muscle cells; Kazuhiro Kishi for 3T3-L1 myc-Glut4 adipocytes; and Morris White for antibodies. This work was supported by a grant from the American Diabetes Association, grants 7-02-JF-26 to Y.-B.K. and 7-01-JF-05 to J.K.K., KOSEF basic research program grant R01-2005-000-10386-0 to Y.H.L., and NIH grants R01 DK43051 to B.B.K. and R01 CA85681 and CA107574 to S.W.L. ",

year = "2005",

month = aug,

doi = "10.1016/j.cmet.2005.06.011",

language = "English",

volume = "2",

pages = "119--129",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "2",

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TY - JOUR

T1 - Role of Rho-kinase in regulation of insulin action and glucose homeostasis

AU - Furukawa, Noboru

AU - Ongusaha, Pat

AU - Jahng, Wan Jin

AU - Araki, Kazushi

AU - Choi, Cheol Soo

AU - Kim, Hyo Jeong

AU - Lee, Yong Hee

AU - Kaibuchi, Kozo

AU - Kahn, Barbara B.

AU - Masuzaki, Hiroaki

AU - Kim, Jason K.

AU - Lee, Sam W.

AU - Kim, Young Bum

N1 - Funding Information: We would like to thank Yasuhiko Minokoshi, Michael Greene, Matthew Brady, and Jean Chan for comments on the manuscript; Jang Youn, Nimesh Mody, Qin Yang, Christian Bjorbaek, Takamasa Higashimori, Mustuki Amano, and Erin Kerstin for technical help; Amira Klip for L6 muscle cells; Kazuhiro Kishi for 3T3-L1 myc-Glut4 adipocytes; and Morris White for antibodies. This work was supported by a grant from the American Diabetes Association, grants 7-02-JF-26 to Y.-B.K. and 7-01-JF-05 to J.K.K., KOSEF basic research program grant R01-2005-000-10386-0 to Y.H.L., and NIH grants R01 DK43051 to B.B.K. and R01 CA85681 and CA107574 to S.W.L.

PY - 2005/8

Y1 - 2005/8

N2 - Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we show that insulin stimulation of glucose transport is impaired when ROK is chemically or biologically inhibited in cultured adipocytes and myotubes and in isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition of ROK activity in mice causes insulin resistance by reducing insulin-stimulated glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. These results strongly suggest that ROK regulates insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an important regulator of insulin signaling and glucose metabolism.

AB - Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action. Recent studies suggest that Rho-kinase (ROK) is a mediator of insulin signaling, via interaction with IRS-1. Here we show that insulin stimulation of glucose transport is impaired when ROK is chemically or biologically inhibited in cultured adipocytes and myotubes and in isolated soleus muscle ex vivo. Inactivation of ROK also reduces insulin-stimulated IRS-1 tyrosine phosphorylation and PI3K activity. Moreover, inhibition of ROK activity in mice causes insulin resistance by reducing insulin-stimulated glucose uptake in skeletal muscle in vivo. Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling. These results strongly suggest that ROK regulates insulin-stimulated glucose transport in vitro and in vivo. Thus, ROK is an important regulator of insulin signaling and glucose metabolism.

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SP - 119

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JO - Cell Metabolism

JF - Cell Metabolism

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ER -

Role of Rho-kinase in regulation of insulin action and glucose homeostasis

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