Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells.
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.
Murata
Masahiro
M
Third Division and Second Division, Department of Medicine and the Department of Basic Allied Medicine, Kobe University School of Medicine, Kobe, Japan.
Okimura
Yasuhiko
Y
Iida
Keiji
K
Matsumoto
Michihiro
M
Sowa
Hideaki
H
Kaji
Hidesuke
H
Kojima
Masayasu
M
Kangawa
Kenji
K
Chihara
Kazuo
K
D000818:Animals; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D054439:Ghrelin; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D008024:Ligands; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D036361:Peptide Hormones; D010455:Peptides / Q000378:metabolism* / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D054439:Ghrelin; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D008024:Ligands; D036361:Peptide Hormones; D010455:Peptides; D010750:Phosphoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one