Polonsky K S, Licinio-Paixao J, Given B D, Pugh W, Rue P, Galloway J, Karrison T, Frank B
J Clin Invest. 1986 Jan;77(1):98-105. doi: 10.1172/JCI112308.
We undertook this study to examine the accuracy of plasma C-peptide as a marker of insulin secretion. The peripheral kinetics of biosynthetic human C-peptide (BHCP) were studied in 10 normal volunteers and 7 insulin-dependent diabetic patients. Each subject received intravenous bolus injections of BHCP as well as constant and variable rate infusions. After intravenous bolus injections the metabolic clearance rate of BHCP (3.8 +/- 0.1 ml/kg per min, mean +/- SEM) was not significantly different from the value obtained during its constant intravenous infusion (3.9 +/- 0.1 ml/kg per min). The metabolic clearance rate of C-peptide measured during steady state intravenous infusions was constant over a wide concentration range. During experiments in which BHCP was infused at a variable rate, the peripheral concentration of C-peptide did not change in proportion to the infusion rate. Thus, the infusion rate of BHCP could not be calculated accurately as the product of the C-peptide concentration and metabolic clearance rate. However, the non-steady infusion rate of BHCP could be accurately calculated from peripheral C-peptide concentrations using a two-compartment mathematical model when model parameters were derived from the C-peptide decay curve in each subject. Application of this model to predict constant infusions of C-peptide from peripheral C-peptide concentrations resulted in model generated estimates of the C-peptide infusion rate that were 101.5 +/- 3.4% and 100.4 +/- 2.8% of low and high dose rates, respectively. Estimates of the total quantity of C-peptide infused at a variable rate over 240 min based on the two-compartment model represented 104.6 +/- 2.4% of the amount actually infused. Application of this approach to clinical studies will allow the secretion rate of insulin to be estimated with considerable accuracy. The insulin secretion rate in normal subjects after an overnight fast was 89.1 pmol/min, which corresponds with a basal 24-h secretion of 18.6 U.
我们开展这项研究以检验血浆C肽作为胰岛素分泌标志物的准确性。在10名正常志愿者和7名胰岛素依赖型糖尿病患者中研究了生物合成人C肽（BHCP）的外周动力学。每位受试者接受了BHCP的静脉推注以及恒速和变速输注。静脉推注后，BHCP的代谢清除率（3.8±0.1 ml/kg每分钟，均值±标准误）与恒速静脉输注期间获得的值（3.9±0.1 ml/kg每分钟）无显著差异。在稳态静脉输注期间测得的C肽代谢清除率在很宽的浓度范围内是恒定的。在以变速输注BHCP的实验中，C肽的外周浓度与输注速率不成比例变化。因此，不能将BHCP的输注速率准确计算为C肽浓度与代谢清除率的乘积。然而，当模型参数从每个受试者的C肽衰减曲线得出时，使用双室数学模型可以从外周C肽浓度准确计算BHCP的非稳态输注速率。应用该模型从外周C肽浓度预测C肽恒速输注，得出的C肽输注速率模型估计值分别为低剂量率和高剂量率的101.5±3.4%和100.4±2.8%。基于双室模型对240分钟内变速输注的C肽总量的估计值为实际输注量的104.6±2.4%。将这种方法应用于临床研究将能够相当准确地估计胰岛素分泌速率。正常受试者禁食过夜后的胰岛素分泌速率为89.1 pmol/分钟，这相当于基础24小时分泌量为18.6 U。
