Dunbar J C, Brown P, Dixon S
Proc Soc Exp Biol Med. 1985 May;179(1):32-7. doi: 10.3181/00379727-179-42060.
The effect of increased levels of growth hormone on glucagon binding by isolated hepatocytes and on the cellular cyclic AMP response to glucagon was evaluated in rats bearing growth hormone-secreting tumor (Mt-T-W15) and in rats treated with rat growth hormone. An increased binding, due to an increased number of receptors, was observed in both groups of animals. Glucagon binding did not correlate with plasma glucagon levels, suggesting a failure of down regulation, possibly due to an effect of growth hormone and insulin on the number of receptors. Tumor-bearing and growth hormone-treated rats had larger hepatocytes so that, when hormone binding was expressed in terms of square micrometer of membrane surface, it appeared decreased. When the tumor was removed the increase in the number of glucagon receptors per cell persisted, even though the average cell size returned toward normal. It is suggested that this retention of the receptors may have been the result of continuing hyperinsulinism. Basal cAMP levels were elevated in hepatocytes of tumor-bearing and growth hormone-treated animals, possibly due to cell hypertrophy. On the other hand, the maximum cAMP response to glucagon was not altered by the experimental procedures. A negative effect of insulin on cAMP accumulation may explain this apparent paradox. Indeed, hepatocytes isolated from rats following tumor removal, but with continuing hyperinsulinemia, had a lower maximum cAMP response, even though the glucagon binding per cell or per unit of cell surface was increased.
在患有分泌生长激素的肿瘤（Mt-T-W15）的大鼠以及用大鼠生长激素处理的大鼠中，评估了生长激素水平升高对分离的肝细胞结合胰高血糖素的影响以及对细胞对胰高血糖素的环磷酸腺苷（cAMP）反应的影响。在两组动物中均观察到由于受体数量增加而导致的结合增加。胰高血糖素结合与血浆胰高血糖素水平不相关，这表明下调失败，可能是由于生长激素和胰岛素对受体数量的影响。患有肿瘤和接受生长激素治疗的大鼠肝细胞较大，因此当以每平方微米膜表面积表示激素结合时，其似乎降低。当切除肿瘤后，尽管平均细胞大小恢复正常，但每个细胞的胰高血糖素受体数量仍持续增加。提示这种受体的保留可能是持续高胰岛素血症的结果。在患有肿瘤和接受生长激素治疗的动物的肝细胞中，基础cAMP水平升高，这可能是由于细胞肥大所致。另一方面，实验程序并未改变对胰高血糖素的最大cAMP反应。胰岛素对cAMP积累的负面影响可能解释了这一明显的矛盾现象。实际上，从切除肿瘤但仍存在高胰岛素血症的大鼠分离的肝细胞，即使每个细胞或每单位细胞表面的胰高血糖素结合增加，其最大cAMP反应也较低。
