Cavallo-Perin P, Bruno A, Nuccio P, Goria M, Pagano G, Lenti G
J Clin Endocrinol Metab. 1986 Oct;63(4):1023-7. doi: 10.1210/jcem-63-4-1023.
Hyperinsulinemia in human cirrhosis is generally considered an expression of reduced hepatic insulin degradation. To determine whether hyperinsulinemia may also depend on an altered feedback inhibition of insulin secretion, we performed euglycemic hyperinsulinemic clamp studies, infusing 40, 372, or 1280 mU/m2 X min biosynthetic human insulin in 30 compensated cirrhotic patients with portal hypertension and impaired glucose tolerance and 25 normal subjects, matched for age, sex, and weight. Mean fasting plasma insulin was significantly higher in cirrhotic patients [26.1 +/- 2.3 vs. 12.4 +/- 0.6 (+/- SE) microU/ml; P less than 0.001], while fasting plasma glucose levels were similar in the 2 groups. The mean plasma C-peptide level was significantly higher in cirrhotic patients, both basally (2.7 +/- 0.1 vs. 1.7 +/- 0.1 ng/ml; P less than 0.001) and during the clamp studies. Suppression of C-peptide at 120 min of the clamp was significantly less in cirrhotic patients (37 +/- 7% vs. 79 +/- 4%, 52 +/- 9% vs. approximately 100%, and 54 +/- 4% vs. approximately 100% during the 40, 372, and 1280 mU/m2 X min insulin infusions, respectively). The fasting C-peptide to insulin molar ratio was significantly lower in cirrhotic patients (5.4 +/- 0.3 vs. 6.4 +/- 0.3; P less than 0.005). The MCR of insulin at the three steady states was not significantly different between the 2 groups, whereas the basal systemic delivery rate of insulin was significantly higher in cirrhotic patients (14.7 +/- 1.7 vs. 6.5 +/- 0.4 mU/m2 X min; P less than 0.001). These results suggest that reduced feedback inhibition of insulin secretion may contribute to the hyperinsulinemia associated with cirrhosis.
人类肝硬化中的高胰岛素血症通常被认为是肝脏胰岛素降解减少的一种表现。为了确定高胰岛素血症是否也可能取决于胰岛素分泌反馈抑制的改变，我们进行了正常血糖高胰岛素钳夹研究，分别以40、372或1280 mU/m2×分钟的速率向30例代偿期肝硬化门静脉高压且糖耐量受损的患者以及25例年龄、性别和体重相匹配的正常受试者输注生物合成人胰岛素。肝硬化患者的空腹血浆胰岛素均值显著更高[26.1±2.3 vs. 12.4±0.6（±SE）μU/ml；P<0.001]，而两组的空腹血糖水平相似。肝硬化患者的血浆C肽均值在基础状态（2.7±0.1 vs. 1.7±0.1 ng/ml；P<0.001）以及钳夹研究期间均显著更高。在钳夹120分钟时，肝硬化患者C肽的抑制程度显著更低（在40、372和1280 mU/m2×分钟胰岛素输注期间，分别为37±7% vs. 79±4%、52±9% vs. 约100%、54±4% vs. 约100%）。肝硬化患者空腹C肽与胰岛素的摩尔比显著更低（5.4±0.3 vs. 6.4±0.3；P<0.005）。两组在三个稳定状态下胰岛素的代谢清除率（MCR）无显著差异，而肝硬化患者胰岛素的基础全身输送率显著更高（14.7±1.7 vs. 6.5±0.4 mU/m2×分钟；P<0.001）。这些结果表明，胰岛素分泌反馈抑制的降低可能导致了与肝硬化相关的高胰岛素血症。
