Bugianesi E, Kalhan S, Burkett E, Marchesini G, McCullough A
Center for Metabolism and Nutrition, Case Western Reserve University, Cleveland, Ohio, USA.
Gastroenterology. 1998 Dec;115(6):1530-40. doi: 10.1016/s0016-5085(98)70033-2.
BACKGROUND & AIMS: Accelerated starvation and early recruitment of alternate fuels in cirrhosis have been attributed to reduced availability of hepatic glycogen. The aim of this study was to measure gluconeogenesis (as a marker of protein oxidation) in relation to total glucose production and glucagon-stimulated glycogenolysis.
Glucose and urea production, gluconeogenesis, and glycogenolysis were calculated using stable isotope methods before and during glucagon infusion (3 ng. kg-1. min-1) in 5 cirrhotic patients and 5 matched controls before and after glycogen repletion.
In the basal state, cirrhotic patients had a normal rate of glucose production, but the contribution of gluconeogenesis was increased (74.3% +/- 4.1% vs. 55. 6% +/- 12.1%; P < 0.005). Glycogen repletion normalized the rate of gluconeogenesis. The glycemic response to glucagon (3 ng. kg-1. min-1) was blunted in cirrhotic patients because of a lower rate of glycogenolysis (0.63 +/- 0.23 vs. 1.22 +/- 0.23 mg. kg-1. min-1; P < 0.01) and was not affected by glycogen repletion. Despite increased gluconeogenesis, the simultaneously measured rate of urea synthesis was lower in cirrhotic patients (3.11 +/- 1.02 vs. 5.0 +/- 1.0 mg/kg; P < 0.05).
These data show that in cirrhosis, glucose production is sustained by an increased rate of gluconeogenesis. The hepatic resistance to glucagon action is not caused by reduced glycogen stores.
肝硬化患者加速饥饿及早期动用替代性能源归因于肝糖原储备减少。本研究旨在测定糖异生（作为蛋白质氧化的标志物）与总葡萄糖生成及胰高血糖素刺激的糖原分解之间的关系。
采用稳定同位素方法，在5例肝硬化患者及5例匹配的对照者糖原补充前后，于输注胰高血糖素（3 ng·kg⁻¹·min⁻¹）前及输注过程中计算葡萄糖和尿素生成、糖异生及糖原分解。
基础状态下，肝硬化患者葡萄糖生成速率正常，但糖异生的贡献增加（74.3%±4.1% 对55.6%±12.1%；P<0.005）。糖原补充使糖异生速率恢复正常。肝硬化患者对胰高血糖素（3 ng·kg⁻¹·min⁻¹）的血糖反应减弱，原因是糖原分解速率较低（0.63±0.23对1.22±0.23 mg·kg⁻¹·min⁻¹；P<0.01），且不受糖原补充的影响。尽管糖异生增加，但同时测定的肝硬化患者尿素合成速率较低（3.11±1.02对5.0±1.0 mg/kg；P<0.05）。
这些数据表明，在肝硬化中，葡萄糖生成通过糖异生速率增加得以维持。肝脏对胰高血糖素作用的抵抗并非由糖原储备减少所致。
