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J Biol Chem. 2002 Feb 15;277(7):5667-74. Epub 2001 Nov 27.

Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells.

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  • 1Third Division and Second Division, Department of Medicine and the Department of Basic Allied Medicine, Kobe University School of Medicine, Kobe, Japan.

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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