LOW-DENSITY LIPOPROTEIN RECEPTOR ACTIVITY IN CULTURED HUMAN-SKIN FIBROBLASTS - MECHANISM OF INSULIN-INDUCED STIMULATION
LOW-DENSITY LIPOPROTEIN RECEPTOR ACTIVITY IN CULTURED HUMAN-SKIN FIBROBLASTS - MECHANISM OF INSULIN-INDUCED STIMULATION
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DOI：
10.1172/jci109587
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发表时间：
1979-01-01
影响因子：
15.9
通讯作者：
ALBERS, JJ
中科院分区：
文献类型：
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作者：
CHAIT, A;BIERMAN, EL;ALBERS, JJ
低密度脂蛋白（LDL）受体的活性，反映了LDL的降解，被添加到人皮肤成纤维细胞培养刺激胰岛素。这些变化的发生与培养培养基的葡萄糖浓度无关，无论LDL受体活性是否受到抑制，这些变化都会发生。在有胰岛素和没有胰岛素的情况下LDL受体活性的饱和动力学比较表明，胰岛素使Vmax增加35%，而表观Km没有差异。胰岛素可能通过增加LDL受体的数量而不是通过影响结合亲和力来增强LDL受体的活性。在构象中，受体阴性细胞对LDL的降解不受胰岛素的促进。胰岛素也刺激了[14C]醋酸酯的固醇合成，但胆固醇的输出和细胞胆固醇含量不受激素的影响。胰岛素对LDL受体的影响并不依赖于其增强细胞DNA合成和增殖的已知能力，因为胰岛素刺激LDL受体活性的细胞通过维持血浆源性血清中缺乏血小板源性生长因子而保持静止。胰岛素在增加LDL受体数量方面的作用，加上对内源性胆固醇合成的刺激，提供了一种机制，在理论上，细胞可以在额外需要时增加胆固醇的供应。
Low-density lipoprotein (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in apparent Km. Insulin may enhance LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In conformation, LDL degradation by receptor-negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet-derived growth factor. The effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need.