Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. |
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Authors: | Masahiro Murata Yasuhiko Okimura Keiji Iida Michihiro Matsumoto Hideaki Sowa Hidesuke Kaji Masayasu Kojima Kenji Kangawa Kazuo Chihara |
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Affiliation: | Third Division and Second Division, Department of Medicine and the Department of Basic Allied Medicine, Kobe University School of Medicine, Kobe, Japan. |
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Abstract: | 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. |
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