Thomopoulos P, Testa U, Gourdin M F, Hervy C, Titeux M, Vainchenker W
Eur J Biochem. 1982 Dec 15;129(2):389-93. doi: 10.1111/j.1432-1033.1982.tb07062.x.
Phorbol esters inhibit the binding of insulin to its receptors on U-937 monocyte-like and HL-60 promyelocytic leukemia human cell lines. Within 20-30 min, exposure of these cells to 12-O-tetradecanoylphorbol 13-acetate (TPA) at 37 degrees C results in a 50% reduction of the specific binding of 125I-insulin. Half-maximal inhibition occurs at 1 nM TPA. Other tumor-promoting phorbol esters also inhibit 125I-insulin binding in a dose-dependent manner which parallels their known promoting activity in vivo. TPA does not alter the degradation of the hormone nor does it induce any shedding of its receptors in the medium. The effect of phorbol esters is dependent on temperature and cell type. It is less prominent at 22 degrees C than at 37 degrees C. It is reversible within 2 h at 37 degrees C. TPA reduces the binding of insulin predominantly by increasing its dissociation rate. This effect results in an accelerated turnover of the hormone on its receptors.
佛波酯可抑制胰岛素与其在U - 937单核细胞样和HL - 60早幼粒细胞白血病人类细胞系上的受体结合。在37℃下，将这些细胞暴露于12 - O - 十四酰佛波醇13 - 乙酸酯（TPA）20 - 30分钟后，125I - 胰岛素的特异性结合减少50%。半最大抑制浓度出现在1 nM TPA时。其他促肿瘤佛波酯也以剂量依赖方式抑制125I - 胰岛素结合，这与其在体内已知的促肿瘤活性平行。TPA不会改变激素的降解，也不会诱导其受体在培养基中脱落。佛波酯的作用取决于温度和细胞类型。在22℃时不如在37℃时明显。在37℃下2小时内该作用是可逆的。TPA主要通过增加胰岛素的解离速率来降低其结合。这种作用导致激素在其受体上的周转加快。
