Wada M, Connolly C C, Tarumi C, Neal D W, Cherrington A D
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Am J Physiol. 1995 Feb;268(2 Pt 1):E194-203. doi: 10.1152/ajpendo.1995.268.2.E194.
In view of the increasing frequency of liver transplantation, and the importance of glucagon in the minute-to-minute regulation of glucose production, we assessed the effect of hepatic denervation on the liver's response to a physiological rise in glucagon in 18-h fasted dogs. Before study (2 wk), the dogs underwent liver denervation (DN; n = 6) or sham operation (SH; n = 5). Endogenous insulin and glucagon secretion were inhibited using somatostatin, and the two hormones were replaced intraportally in basal amounts. After the control period the glucagon infusion rate was tripled for 3 h. Glucagon increased from 41 +/- 8 to 128 +/- 8 and 54 +/- 4 to 129 +/- 9 pg/ml in SH and DN, respectively (P < 0.05), causing tracer-determined glucose production to increase from 2.5 +/- 0.1 to 4.9 +/- 0.5 and 2.3 +/- 0.1 to 5.8 +/- 0.8 mg.kg-1.min-1 by 15 min, respectively (P < 0.05). Glucose clearance fell slightly during glucagon infusion in DN, causing a somewhat greater increase in the plasma glucose level (to 175 +/- 15 vs. 207 +/- 20 mg/dl). The changes in gluconeogenic efficiency increased 65-90% in both groups (P < 0.05). In conclusion, denervation of the liver failed to significantly alter the metabolic response of that organ to a half-maximally effective increment in the plasma glucagon level.
鉴于肝移植频率的增加以及胰高血糖素在葡萄糖生成的每分钟调节中的重要性，我们评估了肝去神经支配对禁食18小时犬肝脏对胰高血糖素生理性升高反应的影响。在研究前（2周），对犬进行肝去神经支配（DN；n = 6）或假手术（SH；n = 5）。使用生长抑素抑制内源性胰岛素和胰高血糖素分泌，并经门静脉以基础量补充这两种激素。在对照期后，将胰高血糖素输注速率提高两倍，持续3小时。在SH组和DN组中，胰高血糖素分别从41±8 pg/ml增加至128±8 pg/ml和从54±4 pg/ml增加至129±9 pg/ml（P < 0.05），导致示踪剂测定的葡萄糖生成在15分钟时分别从2.5±0.1 mg·kg⁻¹·min⁻¹增加至4.9±0.5 mg·kg⁻¹·min⁻¹和从2.3±0.1 mg·kg⁻¹·min⁻¹增加至5.8±0.8 mg·kg⁻¹·min⁻¹（P < 0.05）。在DN组中，胰高血糖素输注期间葡萄糖清除率略有下降，导致血浆葡萄糖水平升高幅度略大（分别升至175±15 mg/dl和207±20 mg/dl）。两组中糖异生效率的变化均增加了65 - 90%（P < 0.05）。总之，肝脏去神经支配未能显著改变该器官对血浆胰高血糖素水平半最大有效增量的代谢反应。
