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 journalArticlepeer-review

119 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 languageEnglish
Pages (from-to)119-129
Number of pages11
JournalCell Metabolism
Volume2
Issue number2
DOIs
Publication statusPublished - 08-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

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