Dept. of Medicine V, Aarhus Univ. Hospital, Denmark.
Am J Physiol Gastrointest Liver Physiol. 2010 Aug;299(2):G486-93. doi: 10.1152/ajpgi.00375.2009. Epub 2010 May 20.
Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7-7.3]. Fasting (f)-insulin increased from 123 +/- 81 to 193 +/- 124 pmol/l (P = 0.03), whereas f-glucose was unchanged (6.0 +/- 0.8 vs. 6.2 +/- 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7-22%) and 53% (CI: 14-90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 +/- 1.82 vs. 4.85 +/- 2.37 mg.kg(-1).min(-1)) and glucose tracer-based rate of disappearance were unchanged (5.01 +/- 1.61 vs. 4.97 +/- 2.13 mg.kg(-1).min(-1)). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 +/- 0.42 vs. 2.42 +/- 0.58 mg.kg(-1).min(-1)) and was suppressed equally by insulin (1.1 +/- 0.1 vs. 1.0 +/- 0.1 mg.kg(-1).min(-1)). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.
经颈静脉肝内门体分流术（TIPS）的插入会增加肝硬化患者的身体细胞质量（BCM）。其负责的机制尚不清楚，但可能涉及胰岛素敏感性和葡萄糖代谢的变化。在 TIPS 手术后 6 个月，通过生物阻抗分析、2 小时口服葡萄糖耐量试验和两步高胰岛素正葡萄糖钳夹术（用示踪剂确定内源性葡萄糖生成）检查了 11 名肝硬化患者。TIPS 后，BCM 增加了 4.8 公斤[置信区间（CI）：2.7-7.3]。空腹（f）-胰岛素从 123 +/- 81 增加到 193 +/- 124 pmol/l（P = 0.03），而空腹血糖不变（6.0 +/- 0.8 与 6.2 +/- 1.0 mmol/l）。口服葡萄糖耐量试验的血糖和胰岛素曲线下面积分别增加了 14%（CI：7-22%）和 53%（CI：14-90%），P < 0.05。C 肽/胰岛素比值下降了 21%（CI：8-35%，P = 0.01）。基于葡萄糖输注率的胰岛素敏感性（4.69 +/- 1.82 与 4.85 +/- 2.37 mg.kg(-1).min(-1)）和基于葡萄糖示踪剂的清除率不变（5.01 +/- 1.61 与 4.97 +/- 2.13 mg.kg(-1).min(-1)）。尽管外周血胰岛素水平进一步升高，但研究日之间的空腹内源性葡萄糖生成没有变化（2.01 +/- 0.42 与 2.42 +/- 0.58 mg.kg(-1).min(-1)），并且对胰岛素的抑制作用相同（1.1 +/- 0.1 与 1.0 +/- 0.1 mg.kg(-1).min(-1)）。胰岛素清除率、生长激素、皮质醇和胰高血糖素水平不变。BCM 的改善与所测量的变量无关。TIPS 后，BCM 升高，尽管存在胰岛素过度分泌和葡萄糖耐量恶化，但外周和肝脏胰岛素敏感性不变。这种明显的差异可能归因于分流相关的胰岛素对肝细胞的暴露减少。然而，TIPS 的合成代谢作用似乎与改善胰岛素敏感性无关，其机制仍未得到解释。
