Chait A, Bierman E L, Albers J J
J Clin Invest. 1979 Nov;64(5):1309-19. doi: 10.1172/JCI109587.
Low-density lipoproteins (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". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, 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. Nevertheless, 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.
低密度脂蛋白（LDL）受体活性，以LDL降解来反映，通过向人皮肤成纤维细胞培养物中添加胰岛素而受到刺激。这些变化独立于孵育培养基的葡萄糖浓度而发生，并且无论LDL受体活性是否受到抑制都会发生。对存在和不存在胰岛素时LDL受体活性的饱和动力学进行比较表明，胰岛素使Vmax增加了35%，而“表观Km”没有差异。这些结果表明，胰岛素通过增加LDL受体的数量而不是通过影响结合亲和力来增强LDL受体活性。经证实，胰岛素不会增强受体阴性细胞对LDL的降解。胰岛素也刺激了由[14C]乙酸盐合成固醇，但胆固醇的流出和细胞胆固醇含量不受该激素影响。胰岛素对LDL受体的作用不依赖于其增强细胞DNA合成和增殖的已知能力，因为胰岛素在维持于不含血小板衍生生长因子的血浆衍生血清中保持静止的细胞中刺激了LDL受体活性。然而，胰岛素在增加LDL受体数量方面的作用，再加上对内源胆固醇合成的刺激，提供了一种机制，理论上细胞可以在额外需要时增加其胆固醇供应。
