肝硬化中糖异生的定量分析：对胰高血糖素的反应

Quantification of gluconeogenesis in cirrhosis: response to glucagon.

作者信息

Bugianesi E, Kalhan S, Burkett E, Marchesini G, McCullough A

机构信息

Center for Metabolism and Nutrition, Case Western Reserve University, Cleveland, Ohio, USA.

出版信息

Gastroenterology. 1998 Dec;115(6):1530-40. doi: 10.1016/s0016-5085(98)70033-2.

DOI:10.1016/s0016-5085(98)70033-2

PMID:9834282

Abstract

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.

摘要

背景与目的

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。

方法

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。

结果

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）。