Arquilla E R, Stenger D, McDougall B, Ulich T R
Department of Pathology, University of California, Irvine 92717.
Diabetes. 1987 Oct;36(10):1144-51. doi: 10.2337/diab.36.10.1144.
The bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies.
在近交系Lewis大鼠中研究了与豚鼠抗血清、纯化的豚鼠IgG1、IgG2、IgG1和IgG2混合物以及同源的Lou/m大鼠抗血清结合的125I标记胰岛素的生物利用度、分布和代谢命运。与纯化的豚鼠IgG2抗体结合的125I胰岛素迅速从血液中清除，并随时间在肝脏中蓄积量增加。与豚鼠IgG1抗体结合的大量125I胰岛素在血液中至少保留30分钟。与IgG1和IgG2抗体结合的125I胰岛素的生物利用度至少被抑制30分钟，因为可用于与肝细胞和肾小管细胞上的胰岛素受体快速结合及其随后快速降解的量明显减少。与单独与纯化的IgG1或IgG2抗体结合的125I胰岛素相比，当与天然豚鼠抗血清或IgG1和IgG2抗体混合物中的抗体结合时，125I胰岛素的生物利用度进一步降低。与天然豚鼠抗血清或IgG1和IgG2抗体混合物中的抗体结合的125I胰岛素在体内的分布方式反映了所存在的IgG1和IgG2抗体的相对浓度。用同源的Lou/m大鼠胰岛素抗血清制备的免疫复合物中125I胰岛素的生物利用度、分布和代谢命运在质量上与用豚鼠胰岛素抗血清制备的免疫复合物中观察到的相似。看来Lewis大鼠可作为体内模型来研究与异种或同源胰岛素抗体结合的胰岛素的生物利用度、分布和代谢命运。
