METABOLISM OF PROINSULIN, INSULIN, AND C-PEPTIDE IN RAT
METABOLISM OF PROINSULIN, INSULIN, AND C-PEPTIDE IN RAT
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DOI：
10.1172/jci107277
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发表时间：
1973-01-01
影响因子：
15.9
通讯作者：
RUBENSTEIN, AH
中科院分区：
文献类型：
--
作者：
KATZ, AI;RUBENSTEIN, AH
研究了大鼠肾脏对牛胰岛素原、胰岛素和c肽的提取和排泄，以及肾脏对它们的总代谢清除率（MCR）的贡献。用恒输注技术测定代谢清除率，用放射免疫法测定各多肽的血浆和尿液浓度。胰岛素的MCR（16.4±0.4 ml/min）显著高于胰岛素原（6.7±0.3 ml/min）和c肽（4.6±0.2 ml/min）。代谢清除率与血浆水平无关，其稳态血浆浓度范围从1到15 ng/ml不等。与代谢清除率的差异相反，这三种多肽的肾脏处置是相似的，其特征是高提取和非常低的尿清除率。胰岛素原、胰岛素和c肽的肾动静脉差值平均分别为36%、40%和44%，与它们的动脉浓度在2 ~ 25 ng/ml之间呈线性相关。当肾小球滤过明显减少或因输尿管梗阻而停止时，胰岛素原、胰岛素和c肽的肾脏提取量总是大于同时测量的菊粉提取量，这表明这些多肽是通过肾小球滤过和直接从小管周围毛细血管血液中摄取而从肾循环中去除的。每种多肽的尿液清除率从未超过0.6%，表明超过99%的过滤量被隔离在肾脏中。肾脏从循环中清除胰岛素原和c肽分别占其代谢耐受率的55%和69%，而肾脏对胰岛素外周代谢的贡献较小，平均为33%。这种差异是由于胰岛素，而不是其他两种多肽，在很大程度上是由肝脏代谢的。这些结果定义了大鼠肾脏对胰岛素原、胰岛素和c肽的处理，并表明肾脏是胰岛素代谢的主要部位，是负责胰岛素原和c肽降解的主要器官。
The renal extraction and excretion of bovine proinsulin, insulin, and C-peptide and the contribution of the kidney to their total metabolic clearance rate (MCR) were studied in the rat. Metabolic clearance rates were measured by the constant infusion technique and plasma and urine concentrations of each polypeptide were determined by radioimmunoassay.The MCR of insulin (16.4±0.4 ml/min) was significantly greater than that of either proinsulin (6.7±0.3 ml/min) or C-peptide (4.6±0.2 ml/min). Metabolic clearance rates were independent of plasma levels over a range of steady-state plasma concentrations varying from 1 to 15 ng/ml.In contrast to the differences in their metabolic clearance rates, the renal disposition of the three polypeptides was similar, being characterized by high extraction and very low urinary clearance. The renal arteriovenous difference of proinsulin, insulin, and C-peptide averaged 36, 40, and 44%, respectively, and was linearly related to their arterial concentration between 2 and 25 ng/ml. When glomerular filtration was markedly reduced or stopped by ureteral obstruction, the renal extraction of proinsulin, insulin, and C-peptide was invariably greater than the simultaneously measured extraction of inulin, indicating that these polypeptides are removed from the renal circulation by both glomerular filtration and direct uptake from peritubular capillary blood. The fractional urinary clearance of each polypeptide never exceeded 0.6%, indicating that more than 99% of the amount filtered was sequestered in the kidney.The renal removal of proinsulin and C-peptide from the circulation accounts for 55 and 69% of their metabolic clerance rates, while the renal contribution to the peripheral metabolism of insulin was smaller, averaging 33%. This difference is due to the fact that insulin, but not the other two polypeptides, is metabolized to a significant extent by the liver. These results define the renal handling of proinsulin, insulin, and C-peptide in the rat and indicate that in this species the kidney represents a major site for insulin metabolism and is the main organ responsible for the degradation of proinsulin and C-peptide.