Montiel F, Aranda A, Pascual A
Unidad de Endocrinologia Experimental, C.S.I.C., Facultad de Medicina, Universidad Autonoma de Madrid, Spain.
Mol Cell Endocrinol. 1989 Feb;61(2):167-74. doi: 10.1016/0303-7207(89)90127-5.
The regulation of the insulin receptor by cAMP has been examined in glial C6 cells. Incubation for 48 h with dibutyryl cyclic AMP produced a dose-dependent inhibition of 125I-insulin binding to the cells. Other agents that elevate intracellular cAMP levels such as forskolin and cholera toxin mimicked the effect of this cyclic AMP analog. With all compounds the maximal decrease of binding was found between 24 and 48 h and normally varied between 40 and 60%. Forskolin, cholera toxin and dibutyryl cyclic AMP also affected C6 cell proliferation, and the dose-response for decreasing the receptor was very similar to that observed for the inhibition of cell growth, suggesting a relationship between both phenomena. Scatchard analysis showed that cAMP did not produce major changes in the affinity of the receptor for insulin, but rather decreased receptor number. An accumulation of receptors at the cell surface was observed in the absence of de novo protein synthesis, since cycloheximide caused a significant increase in insulin binding to the cells. This inhibitor almost totally blocked the cAMP effect both when added simultaneously to the cells with the agents which increase cAMP and when added to cells pre-treated for 48 h with the same compounds.
已在神经胶质C6细胞中研究了cAMP对胰岛素受体的调节作用。用二丁酰环磷酸腺苷（dibutyryl cyclic AMP）孵育48小时会产生剂量依赖性地抑制125I胰岛素与细胞的结合。其他能提高细胞内cAMP水平的试剂，如福斯可林（forskolin）和霍乱毒素，模拟了这种环磷酸腺苷类似物的作用。对于所有化合物，结合的最大减少在24至48小时之间出现，通常在40%至60%之间变化。福斯可林、霍乱毒素和二丁酰环磷酸腺苷也影响C6细胞增殖，并且降低受体的剂量反应与观察到的抑制细胞生长的剂量反应非常相似，表明这两种现象之间存在关联。Scatchard分析表明，cAMP不会使受体对胰岛素的亲和力产生重大变化，而是会减少受体数量。在没有从头合成蛋白质的情况下，观察到细胞表面受体的积累，因为放线菌酮（cycloheximide）会导致胰岛素与细胞的结合显著增加。当与增加cAMP的试剂同时添加到细胞中时，以及当添加到用相同化合物预处理48小时的细胞中时，这种抑制剂几乎完全阻断了cAMP的作用。
