Robert A, Grunberger G, Carpenter J L, Dayer J M, Orci L, Gorden P
Endocrinology. 1984 Jan;114(1):247-53. doi: 10.1210/endo-114-1-247.
Most clinical studies of the insulin receptor in man have been carried out in circulating cells, mainly monocytes. It is important to establish whether the function of the insulin receptor in blood cells reflects that of the major target tissues. Since peripheral monocytes do not divide, they cannot be studied under continuous cell culture conditions. We, therefore, studied the insulin receptor of a monocyte-like human cell line (U-937) to determine whether it could serve as a model for further investigation of the function of the insulin receptor. We found that the U-937 cells bind [125I]insulin specifically and in a time-, temperature-, concentration-, and pH-dependent fashion, similar to circulating monocytes. In addition, they internalize the hormone-receptor complex rapidly and extensively at 37 C in a fashion analogous to that of blood monocytes and hepatocytes. U-937 cells show a similar affinity for insulin as monocytes. Unlike hepatocytes, these cells do not appear to release extensive insulin-degrading activity and do not degrade cell surface-associated ligand during initial incubations. [125I] Insulin extracted or dissociated spontaneously from the cell surface shows full rebindability to fresh cells. The insulin receptor of the U-937 cells can be down-regulated as in the major target cells. As in cultured human lymphocytes, preincubation of U-937 cells with prednisolone results in significantly increased insulin binding. Incubation with a phorbol ester tumor promoter, in contrast, inhibits the extent of specific [125I]insulin binding to U-937 cells by altering the receptor affinity. The insulin receptor of the U-937 monocyte-like cell line mirrors the insulin receptor of blood monocytes and target cells; it is a useful tool for further in vitro studies of the insulin receptor.
大多数关于人类胰岛素受体的临床研究都是在循环细胞中进行的，主要是单核细胞。确定血细胞中胰岛素受体的功能是否反映主要靶组织的功能很重要。由于外周单核细胞不分裂，因此无法在连续细胞培养条件下对其进行研究。因此，我们研究了一种单核细胞样人类细胞系（U-937）的胰岛素受体，以确定它是否可以作为进一步研究胰岛素受体功能的模型。我们发现，U-937细胞以时间、温度、浓度和pH依赖的方式特异性结合[125I]胰岛素，这与循环单核细胞相似。此外，它们在37℃时以类似于血液单核细胞和肝细胞的方式迅速且广泛地内化激素-受体复合物。U-937细胞对胰岛素的亲和力与单核细胞相似。与肝细胞不同，这些细胞在初始孵育期间似乎不会释放大量胰岛素降解活性，也不会降解细胞表面相关配体。从细胞表面自发提取或解离的[125I]胰岛素对新鲜细胞具有完全的再结合能力。U-937细胞的胰岛素受体可以像主要靶细胞一样被下调。与培养的人类淋巴细胞一样，用泼尼松龙预孵育U-937细胞会导致胰岛素结合显著增加。相反，用佛波酯肿瘤启动子孵育会通过改变受体亲和力来抑制[125I]胰岛素与U-937细胞的特异性结合程度。U-937单核细胞样细胞系的胰岛素受体反映了血液单核细胞和靶细胞的胰岛素受体；它是进一步体外研究胰岛素受体的有用工具。
