Jerums G, Hardy K J, Eisman J A
Diabetes. 1977 Feb;26(2):81-8. doi: 10.2337/diab.26.2.81.
The effects of glucagon on tissue and plasma cyclic AMP levels have been investigated in rabbits anesthetized with urethane. Glucagon (2 nmole/kg.) caused at least a twofold increase in hepatic cyclic AMP, which reached a peak within two minutes and declined to basal values after 40 minutes. Plasma cyclic AMP also increased at least twofold, reaching a peak at 10 minutes and declining to basal values after 60 minutes. Glucagon (20 nmole/kg.) stimulated hepatic and plasma cyclic AMP in a manner indistinguishable from that observed at the lower dose. Hepatectomy abolished the plasma cyclic AMP responses to glucagon, and no significant stimulation of cyclic AMP concentration was noted in the heart, adipose tissue, small bowel, or kidney. Cyclic AMP hydrolysis was estimated in blood taken before and after administration of glucagon. Glucagon (2 nmole/kg.) increased cyclic AMP hydrolysis slightly, but this was explained by the raised cyclic AMP levels. By contrast, cyclic AMP hydrolysis increased two-to-threefold in blood taken 20 and 40 minutes after glucagon (20 nmole/kg.). The higher dose of glucagon also stimulated cyclic AMP hydrolysis in crude liver homogenate, which could not be explained by increases in cyclic AMP concentration. The increase in cyclic AMP hydrolysis observed in blood and liver may partly explain the failure to show additional stimulation of hepatic and plasma cyclic AMP levels with the higher dose of glucagon. Despite the changes in cyclic AMP hydrolysis, a highly significant correlation was observed in individual rabbits between the hepatic and plasma cyclic AMP responses to glucagon (2 and 20 nmole/kg.), when these were calculated as incremental areas above mean basal levels. It is suggested that measurement of plasma cyclic AMP levels after stimulation by glucagon may be an accurate index of the hepatic cyclic AMP response to glucagon in vivo.
已在用氨基甲酸乙酯麻醉的兔子身上研究了胰高血糖素对组织和血浆环磷酸腺苷（cAMP）水平的影响。胰高血糖素（2纳摩尔/千克）使肝脏中的环磷酸腺苷至少增加两倍，在两分钟内达到峰值，并在40分钟后降至基础值。血浆环磷酸腺苷也至少增加两倍，在10分钟时达到峰值，并在60分钟后降至基础值。胰高血糖素（20纳摩尔/千克）刺激肝脏和血浆环磷酸腺苷的方式与较低剂量时观察到的无法区分。肝切除消除了血浆环磷酸腺苷对胰高血糖素的反应，并且在心脏、脂肪组织、小肠或肾脏中未观察到对环磷酸腺苷浓度的显著刺激。在给予胰高血糖素前后采集的血液中估计环磷酸腺苷水解情况。胰高血糖素（2纳摩尔/千克）使环磷酸腺苷水解略有增加，但这可以用升高的环磷酸腺苷水平来解释。相比之下，在给予胰高血糖素（20纳摩尔/千克）后20分钟和40分钟采集的血液中，环磷酸腺苷水解增加了两到三倍。较高剂量的胰高血糖素也刺激了粗制肝匀浆中的环磷酸腺苷水解，这无法用环磷酸腺苷浓度的增加来解释。在血液和肝脏中观察到的环磷酸腺苷水解增加可能部分解释了较高剂量的胰高血糖素未能进一步刺激肝脏和血浆环磷酸腺苷水平的原因。尽管环磷酸腺苷水解发生了变化，但在个体兔子中，当将肝脏和血浆环磷酸腺苷对胰高血糖素（2和20纳摩尔/千克）的反应计算为高于平均基础水平的增量面积时，观察到它们之间存在高度显著的相关性。有人提出，胰高血糖素刺激后血浆环磷酸腺苷水平的测量可能是体内肝脏对胰高血糖素的环磷酸腺苷反应的准确指标。
