Immunological properties and biological effectiveness of insulin analogues substituted at position B30
Immunological properties and biological effectiveness of insulin analogues substituted at position B30
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B30 位取代的胰岛素类似物的免疫学特性和生物有效性
DOI：
10.1007/bf00275669
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发表时间：
1984
期刊：
影响因子：
8.2
通讯作者：
G. Schnorr
中科院分区：
文献类型：
--
作者：
H. Neubauer;R. Obermeier;G. Schnorr
本研究的目的是通过检测几种胰岛素类似物的抗原性和免疫原性来评估它们的免疫学特性。此外，还测定了低血糖活性，并与天然胰岛素获得的值进行了比较。改良胰岛素制剂为猪和牛源性。所有类似物的共同点是丙氨酸B30被亮氨酸、苏氨酸、酪氨酸、苯丙氨酸或甘氨酸置换。在兔和犬中测定了降血糖活性，同时在三种不同动物种属（猪、犬和兔）中研究了抗体形成的刺激。通过测量其与预形成抗体的结合能力，在体外评价类似物的抗原特性。在所有情况下，类似物的血糖降低活性与相应天然胰岛素的血糖降低活性相当。有显着差异的结合能力预先形成的抗体，牛Leu-B30胰岛素竞争只有73%的天然胰岛素示踪剂。关于抗体开发，类似物的行为类似于原始激素。这些结果表明，胰岛素分子的抗原组成与其激发抗体刺激的能力之间几乎没有相关性
SummaryThe aim of this investigation was to assess the immunological properties of several insulin analogues by examining both their antigenic and immunogenic behaviour. In addition, the hypoglycaemic activity was also determined and compared with values obtained with natural insulins. The modified insulin preparations were of porcine and bovine origin. All analogues had in common the fact that the alanine B30 had been exchanged by either leucine, threonine, tyrosine, phenylalanine or glycine. The blood glucose-lowering activity was determined in rabbits and dogs, while the stimulation of antibody development was studied in three different animal species; pigs, dogs and rabbits. The antigenic properties of analogues were evaluated in vitro by measuring their binding capacity to pre-formed antibodies. In all cases the blood glucose lowering activity of the analogues was comparable to that of the respective natural insulin. There were remarkable differences in the binding capacity to pre-formed antibodies, with bovine Leu-B30 insulin competing only to 73% with the natural insulin tracer. With regard to antibody development, the analogues behaved similarly to the original hormones. These results show that there is little correlation between the antigenic make-up of the insulin molecule and its ability to provoke antibody stimulation