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J. Biol. Chem., Vol. 277, Issue 7, 5667-5674, February 15, 2002
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From the Ghrelin was identified in the stomach as an
endogenous ligand specific for the growth hormone secretagogue receptor
(GHS-R). GHS-R is found in various tissues, but its function is
unknown. Here we show that GHS-R is found in hepatoma cells. Exposure
of these cells to ghrelin caused up-regulation of several
insulin-induced activities including tyrosine phosphorylation of
insulin receptor substrate-1 (IRS-1), association of the adapter
molecule growth factor receptor-bound protein 2 with IRS-1,
mitogen-activated protein kinase activity, and cell proliferation.
Unlike insulin, ghrelin inhibited Akt kinase activity as well as
up-regulated gluconeogenesis. These findings raise the possibility that
ghrelin modulates insulin activities in humans.
Ghrelin Modulates the Downstream Molecules of Insulin Signaling
in Hepatoma Cells*
,,
,,**,,, and
Third Division and Second Division,
Department of Medicine and the § Department of Basic Allied
Medicine, Kobe University School of Medicine, Kobe, 650-0017, the
** College of Nursing Art and Science, Hyogo, Akashi
673-8588, and the Department of
Biochemistry, National Cardiovascular Center Research Institute, Suita,
Osaka 565-8565, Japan
*
This work was supported by a grant-in-aid for scientific
research from the Japanese ministry of Education, Science, and Culture and by grants from the Japanese Ministry of Health, Labor, And Welfare
and the Foundation for Growth Science in Japan.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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