Walsh M F, Dunbar J C
Diabetes. 1984 Oct;33(10):978-83. doi: 10.2337/diab.33.10.978.
To assess the effect of the endocrine environment and, more specifically, of growth hormone and insulin on glucagon receptors, we studied 125I-glucagon binding to liver membranes in five groups of rats: (1) controls, (2) streptozocin (STZ)-treated, (3) tumor-bearing (growth hormone-producing, Mt-T-W15), (4) STZ-treated tumor-bearing, and (5) hypophysectomized rats. Glucagon binding was decreased in tumor-bearing, hypophysectomized, and STZ-treated rats. Basal and glucagon-stimulated cAMP levels were determined in isolated hepatocytes. The basal cAMP levels were increased in STZ-treated, tumor-bearing, STZ-treated tumor-bearing, and hypophysectomized animals. All groups responded and produced more cAMP in response to glucagon stimulation, although the maximal response was greater in STZ-treated, tumor-bearing STZ-treated, and hypophysectomized groups than in the controls. Our data confirm that hyperglucagonemia downregulates the hepatic glucagon receptors and suggest that insulin and growth hormone may play a stimulatory role in their regulation. The results also suggest that the downregulation of glucagon receptors is not directly correlated to the basal or glucagon-stimulated cAMP levels.
为评估内分泌环境，更具体地说是生长激素和胰岛素对胰高血糖素受体的影响，我们在五组大鼠中研究了125I-胰高血糖素与肝细胞膜的结合情况：（1）对照组，（2）链脲佐菌素（STZ）处理组，（3）荷瘤组（产生生长激素的Mt-T-W15），（4）STZ处理的荷瘤组，以及（5）垂体切除大鼠组。在荷瘤、垂体切除和STZ处理的大鼠中，胰高血糖素结合减少。在分离的肝细胞中测定基础和胰高血糖素刺激的cAMP水平。在STZ处理组、荷瘤组、STZ处理的荷瘤组和垂体切除组动物中，基础cAMP水平升高。所有组对胰高血糖素刺激均有反应并产生更多cAMP，尽管在STZ处理组、荷瘤STZ处理组和垂体切除组中的最大反应大于对照组。我们的数据证实高胰高血糖素血症会下调肝脏胰高血糖素受体，并表明胰岛素和生长激素可能在其调节中起刺激作用。结果还表明，胰高血糖素受体的下调与基础或胰高血糖素刺激的cAMP水平无直接相关性。
