Harmon J T, Hilf R
Biochim Biophys Acta. 1976 Aug 4;443(1):114-25. doi: 10.1016/0005-2736(76)90495-8.
Dissociated cells of the R3230AC mammary tumor were found to take up glucose by diffusion and by a passive carrier system. Using labeled 3-O-methylglucose as the probe, the following properties of the passive carrier were identified: (1) specificity for glucose, (2) competition by galactose and mannose but not by mannitol and fructose, (3) inhibition by phloretin but not by phloridzin, (4) temperature sensitivity, and (5) a Km for transport of 3-4 mM. The effects of insulin in vitro on carrier-mediated glucose transport were investigated in tumor cells from diabetic rats. At 10-9 M insulin, a time-related decrease in v for transport was observed resulting in an increased calculated Km (2- to 3-fold increase after 60-90 min incubation with insulin); only slight effects on V were obtained. This unusual response in v to insulin was observed when glucose was present in the medium at 2 mM and 5 mM, but not at 20 mM glucose. The effect of insulin to decrease the v was dose-related, with the major effects seen between 10-10M and 10-8M. The apparent decrease in glucose entry in vitro may in part explain the ability of insulin to inhibit growth of this tumor in vivo.
研究发现，R3230AC乳腺肿瘤的解离细胞可通过扩散和被动载体系统摄取葡萄糖。以标记的3-O-甲基葡萄糖作为探针，确定了被动载体的以下特性：（1）对葡萄糖的特异性；（2）半乳糖和甘露糖可竞争，但甘露醇和果糖不能竞争；（3）根皮素可抑制，但根皮苷不能抑制；（4）温度敏感性；（5）转运的Km为3 - 4 mM。在糖尿病大鼠的肿瘤细胞中研究了体外胰岛素对载体介导的葡萄糖转运的影响。在10^-9 M胰岛素浓度下，观察到转运速度v随时间下降，导致计算出的Km增加（与胰岛素孵育60 - 90分钟后增加2至3倍）；对V只有轻微影响。当培养基中葡萄糖浓度为2 mM和5 mM时，观察到v对胰岛素的这种异常反应，但葡萄糖浓度为20 mM时未观察到。胰岛素降低v的作用与剂量相关，主要作用在10^-10M至10^-8M之间。体外葡萄糖摄取的明显减少可能部分解释了胰岛素在体内抑制该肿瘤生长的能力。
