Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells
Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells
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DOI：
10.1074/jbc.m103898200
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发表时间：
2002-02-15
影响因子：
4.8
通讯作者：
Chihara, K
中科院分区：
文献类型：
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作者：
Murata, M;Okimura, Y;Chihara, K
胃饥饿素在胃中被鉴定为生长激素促分泌受体（GHS-R）的内源性配体。GHS-R存在于多种肿瘤中，但其功能尚不清楚。我们发现GHS-R存在于肝癌细胞中。这些细胞暴露于胃饥饿素导致胰岛素诱导的多种活性上调，包括胰岛素受体底物-1 （IRS-1）的酪氨酸磷酸化、适配器分子生长因子受体结合蛋白2与IRS-1的关联、丝裂原激活的蛋白激酶活性和细胞增殖。与胰岛素不同，胃饥饿素抑制Akt激酶活性并上调糖异生。这些发现提高了胃饥饿素调节人体内胰岛素活动的可能性。
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 tis- sues, 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.