Hamberg O, Vilstrup H
Department of Medicine A-2151, Division of Hepatology Rigshospitalet, Copenhagen, Denmark.
Clin Nutr. 1994 Jun;13(3):183-91. doi: 10.1016/0261-5614(94)90099-x.
The separate effects of glucose and glucagon on alanine stimulated hepatic amino-N to urea-N conversion, quantified by the Functional Hepatic Nitrogen Clearance (FHNC) (i.e. the linear slope of the relation between urea synthesis rate and blood alpha-amino-N concentration), were studied in 7 healthy subjects. FHNC was measured four times in each: during constant infusion of alanine alone; alanine superimposed on constant glucose infusion; alanine superimposed on glucose and low stepwise glucagon infusions; and alanine super-imposed on glucose and high constant glucagon infusions. Glucose halved the glucagon response to alanine. This reduction was abolished by the low stepwise glucagon infusion, aimed at re-establishing portal glucagon levels. The high glucagon infusion resulted in 3-fold elevated glucagon levels. During alanine infusion alone FHNC was (mean +/- SEM) 32.5 +/- 1.9 l/h. Glucose reduced FHNC by 43% to 18.4 +/- 0.9 l/h (p < 0.01). The low stepwise glucagon infusion only partially normalized FHNC as reduced by glucose (to 24.6 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The high glucagon infusion increased FHNC by 35% despite hyperglycaemia (to 44.1 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The results show that both glucose and glucagon are independent but opposite regulators of hepatic amino-N conversion. The physiological glucose effect is accomplished by a combination of both the effect of glucose itself and the inhibition by glucose of the glucagon response to alanine. Hyperglucagonaemia increases FHNC and overrules the inhibition by glucose. This may explain the defect nitrogen sparing by glucose and to some extent the catabolism in hyperglucagonaemic stress conditions, despite prevailing hyperglycaemia.
通过功能性肝氮清除率（FHNC）（即尿素合成速率与血液α-氨基氮浓度之间关系的线性斜率）来量化葡萄糖和胰高血糖素对丙氨酸刺激的肝脏氨基氮向尿素氮转化的单独影响，在7名健康受试者中进行了研究。在每个受试者中测量FHNC四次：单独持续输注丙氨酸期间；丙氨酸叠加在持续葡萄糖输注上；丙氨酸叠加在葡萄糖和低剂量逐步增加的胰高血糖素输注上；以及丙氨酸叠加在葡萄糖和高剂量持续胰高血糖素输注上。葡萄糖使胰高血糖素对丙氨酸的反应减半。通过旨在恢复门静脉胰高血糖素水平的低剂量逐步增加的胰高血糖素输注，这种降低被消除。高剂量胰高血糖素输注导致胰高血糖素水平升高3倍。在单独输注丙氨酸期间，FHNC为（平均值±标准误）32.5±1.9升/小时。葡萄糖使FHNC降低43%至18.4±0.9升/小时（p<0.01）。低剂量逐步增加的胰高血糖素输注仅部分使被葡萄糖降低的FHNC恢复正常（至24.6±1.5升/小时，（与单独输注丙氨酸相比，p<0.01））。尽管存在高血糖，高剂量胰高血糖素输注仍使FHNC增加35%（至44.1±1.5升/小时，（与单独输注丙氨酸相比，p<0.01））。结果表明，葡萄糖和胰高血糖素都是肝脏氨基氮转化的独立但相反的调节因子。生理上的葡萄糖效应是通过葡萄糖本身的作用以及葡萄糖对胰高血糖素对丙氨酸反应的抑制作用共同实现的。高胰高血糖素血症会增加FHNC并克服葡萄糖的抑制作用。这可能解释了尽管存在高血糖，但在高胰高血糖素血症应激条件下葡萄糖的氮节约缺陷以及某种程度上的分解代谢。
