Modulation of insulin activities by leptin
Modulation of insulin activities by leptin
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DOI：
10.1126/science.274.5290.1185
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发表时间：
1996-11-15
期刊：
影响因子：
56.9
通讯作者：
Rubinstein, M
中科院分区：
文献类型：
--
作者：
Cohen, B;Novick, D;Rubinstein, M
瘦素通过其受体OB-R的下丘脑形式介导其对食物摄入的影响。OB-R的变体在其他组织中也有发现，但其功能尚不清楚。在这里，在人类肝细胞中发现了OB-R变体。这些细胞暴露于瘦素，在与肥胖个体中存在的浓度相当的浓度下，引起几种胰岛素诱导的活动的衰减，包括胰岛素受体底物-1（IRS-1）的酪氨酸磷酸化，接头分子生长因子受体结合蛋白2与IRS-1的关联，以及对胰岛素生成的下调。与此相反，瘦素增加IRS-1相关的磷脂酰肌醇3-激酶的活性。这些体外研究提高了瘦素调节肥胖个体胰岛素活性的可能性。
Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.