Cedars-Sinai Diabetes and Obesity Research Institute , Los Angeles, California.
Cedars-Sinai Medical Center, Department of Surgery , Los Angeles, California.
Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E605-E612. doi: 10.1152/ajpendo.00344.2017. Epub 2018 Mar 6.
Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to estimate the clearance of insulin, which is assumed to reflect FPE. We compared two methodologically different but commonly used indirect estimates with directly measured FPE in healthy dogs ( n = 9). The indirect methods were 1) metabolic clearance rate of insulin (MCR) during the hyperinsulinemic-euglycemic clamp (EGC), a steady-state method, and 2) fractional clearance rate of insulin (FCR) during the frequently sampled intravenous glucose tolerance test (FSIGT), a dynamic method. MCR was calculated as the ratio of insulin infusion rate to steady-state plasma insulin. FCR was calculated as the exponential decay rate constant of the injected insulin. Directly measured FPE is based on the difference in insulin measurements during intraportal vs. peripheral vein insulin infusions. We found a strong correlation between indirect FCR (min) and FPE (%). In contrast, we observed a poor association between MCR (ml·min·kg) and FPE (%). Our findings in canines suggest that FCR measured during FSIGT can be used to estimate FPE. However, MCR calculated during EGC appears to be a poor surrogate for FPE.
高胰岛素血症伴随着第一通过肝脏胰岛素提取（FPE）的减少和分泌的增加，是对胰岛素抵抗的主要反应。不同的体内方法用于估计胰岛素的清除率，这被认为反映了 FPE。我们在健康犬（n=9）中比较了两种方法学上不同但常用的间接估计与直接测量的 FPE。间接方法是 1）高胰岛素-正常血糖钳夹（EGC）期间的胰岛素代谢清除率（MCR），一种稳态方法，和 2）频繁采样静脉葡萄糖耐量试验（FSIGT）期间的胰岛素分数清除率（FCR），一种动态方法。MCR 计算为胰岛素输注率与稳态血浆胰岛素的比值。FCR 计算为注射胰岛素的指数衰减率常数。直接测量的 FPE 基于门静脉内与外周静脉胰岛素输注期间胰岛素测量值的差异。我们发现间接 FCR（min）和 FPE（%）之间存在很强的相关性。相比之下，我们观察到 MCR（ml·min·kg）和 FPE（%）之间的相关性较差。我们在犬中的发现表明，FSIGT 期间测量的 FCR 可用于估计 FPE。然而，EGC 期间计算的 MCR 似乎是 FPE 的一个不良替代物。
