QUANTITATIVE ASPECTS OF THE REACTION BETWEEN INSULIN AND INSULIN-BINDING ANTIBODY
QUANTITATIVE ASPECTS OF THE REACTION BETWEEN INSULIN AND INSULIN-BINDING ANTIBODY
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DOI：
10.1172/jci103979
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发表时间：
1959-01-01
影响因子：
15.9
通讯作者：
YALOW, RS
中科院分区：
文献类型：
--
作者：
BERSON, SA;YALOW, RS
本文介绍了一价或多价抗原与单级或多级抗体结合位点反应的系统中平衡态和瞬态数据的分析和评价方法。平衡态和瞬态研究揭示了胰岛素-抗体复合物的异质性。从各种实验方法的结果来看，胰岛素在与抗体的反应中是单价的，并且在大多数抗血清中存在（至少）2级抗体结合位点（“a”和“b”），“a”术语指的是与胰岛素有更大亲和力的位点。胰岛素的单价性不一定等同于单抗原性，因为在不同可能的抗原性位点上结合一个以上的抗体分子可能被位阻所禁止。给出了平衡常数和正、反向速度常数的实验值。非胰岛素抵抗组（低抗体浓度）血清的平衡常数通常显著高于胰岛素抵抗组（高抗体浓度）。这些发现表明胰岛素结合抗体合成速率的增加可能与对抗原亲和力较低的抗体的产生有关。抗体位点为a和b的反应的标准自由能变化分别在- 11 ~ 14 kcal / mol和- 10 ~ 11 kcal / mol之间。初步数据表明，在胰岛素-抗体复合物的形成过程中，热量含量的变化约为每摩尔3.5千卡，熵的正变化为25至30熵单位。本文简要讨论了这些研究结果与临床胰岛素抵抗某些方面的关系。
Methods are presented for the analysis and evaluation of equilibrium state and transient state data in systems composed of univalent or multivalent antigens reacting with a single order or with multiple orders of antibody combining-sites. Heterogeneity of insulin-antibody complexes is revealed by both equilibrium state and transient state studies. It appears, from the results of a variety of experimental approaches, that insulin is univalent in its reaction with antibody and that there are (at least) 2 orders of antibody combining-sites ("a" and "b") present in most antiserums, the "a" term being given to the sites with the greater affinity for insulin., Univalency of insulin is not necessarily to be equated with mono-antigenicity inasmuch as binding of more than a single antibody molecule at different possible antigenic sites is conceivably prohibited by steric hindrance. Experimental values are given for equilibrium constants and forward and reverse velocity constants. The equilibrium constants were generally significantly higher in serums of nonresistant subjects (low antibody concentrations) than in serums of insulin resistant subjects (high antibody concentrations). These findings imply that an increased rate of synthesis of insulin-binding antibody may be associated with the production of antibody of lower affinity for the antigen. The standard free energy changes for the reactions with "a" and "b" antibody sites are in the range, minus 11 to 14 kcal per mole and minus 10 to 11 kcal per mole, respectively. Preliminary data indicate a change in heat content of about 3.5 kcal per mole and a positive entropy change of 25 to 30 entropy units in the formation of insulin-antibody complexes. The relationship of the results of these studies to certain aspects of clinical insulin resistance is considered briefly.