Polonsky K, Jaspan J, Pugh W, Cohen D, Schneider M, Schwartz T, Moossa A R, Tager H, Rubenstein A H
J Clin Invest. 1983 Sep;72(3):1114-23. doi: 10.1172/JCI111036.
The in vivo hepatic metabolism of connecting peptide (C-peptide) in relation to that of insulin has not been adequately characterized. A radioimmunoassay for dog C-peptide was therefore developed and its metabolism studied in conscious mongrel dogs, with sampling catheters chronically implanted in their portal and hepatic veins and femoral artery. The hepatic extraction of endogenous C-peptide under basal conditions was negligible (4.3 +/- 4.5%) and was similar to the hepatic extraction of C-peptide measured during the constant exogenous infusion of C-peptide isolated from dog pancreas. Simultaneously measured hepatic extraction of endogenous and exogenously infused insulin were 43.8 +/- 7.6 and 47.5 +/- 4.4%, respectively. The metabolic clearance rate of infused C-peptide was 11.5 +/- 0.8 ml/kg per min and was constant over the concentration range usually encountered under physiological conditions. In additional experiments, the effect of parenteral glucose administration on the hepatic extraction of C-peptide and insulin was investigated. The hepatic extraction of C-peptide (6.2 +/- 4.0%) was again negligible in comparison with that of insulin (46.7 +/- 3.4%). Parenteral glucose administration did not affect the hepatic extraction of either peptide irrespective of whether it was infused peripherally, intraportally, or together with an intraportal infusion of gastrointestinal inhibitory polypeptide. The fasting C-peptide insulin molar ratio in both the portal vein (1.2 +/- 0.1) and femoral artery (2.1 +/- 0.3) was also unaffected by the glucose stimulus. These results therefore indicate that, since the hepatic extraction of C-peptide is negligible and its clearance kinetics linear, the peripheral C-peptide concentration should accurately reflect the rate of insulin secretion. New approaches to the quantitation of hepatic extraction and secretion of insulin by noninvasive techniques are now feasible.
连接肽（C肽）在体内的肝脏代谢及其与胰岛素代谢的关系尚未得到充分阐明。因此，我们开发了一种犬C肽放射免疫分析法，并在清醒的杂种犬中研究其代谢情况，这些犬通过长期植入门静脉、肝静脉和股动脉的采样导管进行采样。基础条件下内源性C肽的肝脏摄取可忽略不计（4.3±4.5%），与持续外源性输注从犬胰腺分离的C肽时测得的肝脏摄取相似。同时测得的内源性和外源性输注胰岛素的肝脏摄取分别为43.8±7.6%和47.5±4.4%。输注C肽的代谢清除率为11.5±0.8 ml/kg每分钟，在生理条件下通常遇到的浓度范围内保持恒定。在额外的实验中，研究了胃肠外给予葡萄糖对C肽和胰岛素肝脏摄取的影响。与胰岛素（46.7±3.4%）相比，C肽的肝脏摄取（6.2±4.0%）再次可忽略不计。无论胃肠外给予葡萄糖是经外周、门静脉内输注，还是与门静脉内输注胃肠抑制多肽一起给予，均不影响两种肽的肝脏摄取。葡萄糖刺激也不影响门静脉（1.2±0.1）和股动脉（2.1±0.3）中空腹C肽胰岛素摩尔比。因此，这些结果表明，由于C肽的肝脏摄取可忽略不计且其清除动力学呈线性，外周C肽浓度应能准确反映胰岛素分泌速率。现在，通过非侵入性技术定量肝脏摄取和分泌胰岛素的新方法是可行的。
