Gluconeogenesis from Alanine in Normal Postabsorptive Man: Intrahepatic Stimulatory Effect of Glucagon
Gluconeogenesis from Alanine in Normal Postabsorptive Man: Intrahepatic Stimulatory Effect of Glucagon
复制标题
正常吸收后人体内丙氨酸的糖异生：胰高血糖素的肝内刺激作用
作者：
J. Chiasson;J. Liljenquist;B. Sinclair;W. Lacy
虽然胰高血糖素对糖异生的刺激作用已经在体外的某些系统中得到了很好的证明，但这种作用从未在人体中得到证实。因此，本研究旨在确定胰高血糖素是否能刺激正常空腹男性丙氨酸的糖异生。胰高血糖素可能通过增加肝脏丙氨酸摄取和/或通过将肝脏内提取的丙氨酸分流到糖异生途径来刺激这一过程。为了能够检查这两个方面的糖异生，我们结合肝静脉肱动脉导管技术与丙氨酸- 14c同位素输注。采用快速色谱法测定全血和血浆中丙氨酸- 14c的比活性。由于血浆贡献了93%的由内脏床提取的丙氨酸，其比活性是红细胞的三倍，血浆丙氨酸比活性用于研究丙氨酸向葡萄糖的转化。持续输注丙氨酸- 14c可在40分钟内获得相对稳定的动脉比活性。持续输注胰高血糖素（15-50 ng./kg./min）对内脏提取谷丙氨酸无影响。然而，胰高血糖素输注期间，净内脏葡萄糖- 14c产量增加了一倍，丙氨酸转化为葡萄糖的量从30±2 μmol/min增加到58±9 μmol/min。这些数据(1)表明，在禁食12至14小时的正常人中，超生理水平的胰高血糖素可以使丙氨酸的糖异生速率加倍；(2)表明，胰高血糖素的刺激作用是通过将提取的丙氨酸分流到新的葡萄糖形成中，而不是通过增加肝脏对丙氨酸的提取来发挥作用。
Although the stimulatory effect of glucagon on gluconeogenesis has been well demonstrated in certain systems in vitro, this effect has never been established in man. The present study was undertaken, therefore, to determine whether glucagon could stimulate gluconeogenesis from alanine in normal fasting man. Glucagon might stimulate this process by increasing the hepatic alanine uptake and/or by shunting the extracted alanine within the liver into the gluconeogenic pathway. In order to be able to examine these two aspects of gluconeogenesis, we combined the hepatic veinbrachial artery catheterization technic with an isotopic infusion of alanine-14C. Alanine-14C specific activity was measured in whole blood and plasma by use of a rapid chromatographic technic. Since plasma contributed 93 per cent of the alanine extracted by the splanchnic bed with a specific activity three times that of the red blood cells, plasma alanine specific activity was used to study the conversion of alanine to glucose. A constant infusion of alanine-14C achieved a relatively stable arterial specific activity by forty minutes. The administration of glucagon by constant infusion (15–50 ng./kg./min.) had no effect on the splanchnic extraction of alanine. Net splanchnic glucose-14C production, however, doubled during the glucagon infusion, and the conversion of alanine to glucose increased from 30 ± 2 to 58 ± 9 μmol/min. These data (1) demonstrate that in normal man fasted twelve to fourteen hours, glucagon at supraphysiblogic levels can double the rate of gluconeogenesis from alanine and (2) indicate that this stimulatory effect of glucagon is exerted within the liver by shunting the extracted alanine toward new glucose formation rather than by increasing the hepatic extraction of alanine.