Shmueli E, Walker M, Alberti G, Record C O
Gastroenterology and Liver Unit, Royal Victoria Infirmary, University of Newcastle Upon Tyne, United Kingdom.
Hepatology. 1993 Jul;18(1):86-95.
The site of impaired glucose uptake in cirrhosis is uncertain. We therefore performed hyperglycemic clamps (glucose 10 mmol/L) in 10 patients with compensated alcoholic cirrhosis and impaired glucose tolerance and in six control subjects. Muscle glucose uptake was estimated in patients and controls with the forearm technique. In the cirrhotic subjects splanchnic glucose uptake was measured with hepatic vein catheterization and primed continuous infusions of indocyanine green and [6-3H]glucose. To assess insulin-independent glucose uptake and the effects of elevated nonesterified fatty acid levels on glucose uptake, we repeated the study with somatostatin to induce insulin deficiency and a nicotinic acid analog, acipimox, to inhibit lipolysis. Substrate disposal was assessed on indirect calorimetry. Despite similar stimulated insulin levels, total glucose utilization was lower in the cirrhotic subjects (3.9 +/- 0.3 vs. 8.8 +/- 1.7 mg/kg/min, p = 0.006). This deficiency was accounted for by lower nonoxidative glucose disposal (1.2 +/- 0.2 vs. 5.8 +/- 1.6 mg/kg/min, p = 0.002). Forearm glucose uptake was lower in the cirrhotic subjects (0.39 +/- 0.06 vs. 1.21 +/- 0.3 mg/100 ml/min, p = 0.001). However, splanchnic glucose uptake at 1.59 +/- 0.14 mg/kg/min was similar to that reported in other studies of normal subjects. Insulin-independent glucose uptake was normal, and acipimox had no effect on total or forearm glucose utilization. Glucose intolerance in cirrhosis is characterized by impaired peripheral insulin-stimulated non-oxidative glucose disposal. The high nonesterified fatty acid levels seen in cirrhosis most likely do not contribute to this defect. Splanchnic glucose uptake is normal in cirrhosis.
肝硬化患者葡萄糖摄取受损的部位尚不确定。因此，我们对10例代偿期酒精性肝硬化且糖耐量受损的患者以及6例对照者进行了高血糖钳夹试验（葡萄糖浓度为10 mmol/L）。采用前臂技术评估患者和对照者的肌肉葡萄糖摄取情况。对于肝硬化受试者，通过肝静脉插管以及吲哚菁绿和[6-³H]葡萄糖的首剂连续输注来测量内脏葡萄糖摄取。为了评估胰岛素非依赖型葡萄糖摄取以及非酯化脂肪酸水平升高对葡萄糖摄取的影响，我们使用生长抑素诱导胰岛素缺乏，并使用烟酸类似物阿西莫司抑制脂肪分解，重复了该研究。通过间接测热法评估底物处置情况。尽管刺激后的胰岛素水平相似，但肝硬化受试者的总葡萄糖利用率较低（3.9±0.3 vs. 8.8±1.7 mg/kg/min，p = 0.006）。这种不足是由于非氧化葡萄糖处置较低（1.2±0.2 vs. 5.8±1.6 mg/kg/min，p = 0.002）。肝硬化受试者的前臂葡萄糖摄取较低（0.39±0.06 vs. 1.21±0.3 mg/100 ml/min，p = 0.001）。然而，内脏葡萄糖摄取为1.59±0.14 mg/kg/min，与其他正常受试者研究中报告的相似。胰岛素非依赖型葡萄糖摄取正常，阿西莫司对总葡萄糖或前臂葡萄糖利用率无影响。肝硬化患者的糖耐量异常表现为外周胰岛素刺激的非氧化葡萄糖处置受损。肝硬化中所见的高非酯化脂肪酸水平很可能与这一缺陷无关。肝硬化患者的内脏葡萄糖摄取正常。
