Arquilla E R, McDougall B R, Stenger D P
Department of Pathology, University of California, Irvine 92717.
Diabetes. 1989 Mar;38(3):343-9. doi: 10.2337/diab.38.3.343.
The in vivo bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to isologous and autologous antibodies were studied in inbred Lou/M rats. There was an impaired bioavailability of the 125I-insulin bound to the isologous and autologous antibodies. Very little of the 125I-insulin in these immune complexes could bind to insulin receptors on hepatocytes or renal tubular cells and be degraded, because the amounts of 125I from degraded 125I-insulin in the blood or secreted into the stomach were markedly attenuated in both cases for at least 30 min after injection. There was a simultaneous accumulation of 125I-insulin immune complexes in the liver and the kidneys of Lou/M rats injected with 125I-insulin complexed with isologous antibodies or when insulin-immunized Lou/M rats were injected with 125I-insulin during the same interval. The impaired bioavailability of immune-complexed insulin and altered distribution of radioactivity due to the accumulation of immune complexes in the liver and kidney were also observed in previous experiments in which Lewis rats were injected with xenogenic guinea pig and homologous insulin antibodies. These observations are therefore submitted as evidence that the Lou/M rat is a valid model in which to study the bioavailability of insulin immune complexed to isologous, homologous, and xenogenic antibodies and the metabolic fate of the respective insulin-antibody immune complexes.
在近交系Lou/M大鼠中研究了与同种和自身抗体复合的125I标记胰岛素的体内生物利用度、分布及代谢命运。与同种和自身抗体结合的125I胰岛素的生物利用度受损。这些免疫复合物中的125I胰岛素很少能与肝细胞或肾小管细胞上的胰岛素受体结合并被降解，因为在注射后至少30分钟内，两种情况下血液中降解的125I胰岛素或分泌到胃中的125I胰岛素的量均明显减少。在注射与同种抗体复合的125I胰岛素的Lou/M大鼠肝脏和肾脏中，或者在相同时间段内对胰岛素免疫的Lou/M大鼠注射125I胰岛素时，会同时出现125I胰岛素免疫复合物的蓄积。在之前将Lewis大鼠注射异种豚鼠和同源胰岛素抗体的实验中，也观察到了免疫复合物结合胰岛素的生物利用度受损以及由于免疫复合物在肝脏和肾脏中蓄积导致的放射性分布改变。因此，这些观察结果作为证据表明，Lou/M大鼠是研究与同种、同源和异种抗体复合的胰岛素生物利用度以及相应胰岛素 - 抗体免疫复合物代谢命运的有效模型。
