Shimizu F, Hooks J J, Kahn C R, Notkins A L
J Clin Invest. 1980 Nov;66(5):1144-51. doi: 10.1172/JCI109944.
Viral infections may produce abnormalities in carbohydrate metabolism in normal subjects and profound changes in glucose homeostasis in insulin-dependent diabetics. Using an in vitro radio-receptor assay with 125I-labeled insulin and human-amnion (WISH) cells, the effect of viral infections on insulin receptors was examined. Both herpes simplex virus and vesicular stomatitis virus produced a 50% decrease in insulin binding. There was no evidence that this decrease was due to degradation of insulin. On quantitative analysis, this decrease in binding was found to be the result of a decrease in receptor concentration with no change in receptor affinity. The decrease in receptors occurred between 4 and 12 h, at the time viral antigens were being inserted into the plasma membrane of infected cells. Because the t 1/2 of insulin receptors in uninfected cells was between 14 and 24 h, the decrease in insulin receptors cannot be explained solely by virus-induced shut-off of macromolecular synthesis. Moreover, viruses such as encephalomyocarditis that do not insert new antigens into the plasma membrane, did not cause changes in the number of insulin receptors. The most likely explanation is that virus-induced changes in the plasma membrane altered or displaced insulin receptors. It is concluded that the insulin receptor assay is a sensitive and quantitative method for studying the effect of viral infections on cell membranes. These data also suggest that abnormalities in glucose metabolism associated with some viral infections may be due, in part, to changes in the concentration of insulin receptors.
病毒感染可能会使正常受试者的碳水化合物代谢出现异常，并使胰岛素依赖型糖尿病患者的葡萄糖稳态发生显著变化。利用125I标记的胰岛素和人羊膜（WISH）细胞进行体外放射受体测定，研究了病毒感染对胰岛素受体的影响。单纯疱疹病毒和水疱性口炎病毒均使胰岛素结合减少了50%。没有证据表明这种减少是由于胰岛素降解所致。经定量分析，发现这种结合减少是受体浓度降低的结果，而受体亲和力没有变化。受体减少发生在4至12小时之间，此时病毒抗原正插入受感染细胞的质膜。由于未感染细胞中胰岛素受体的半衰期在14至24小时之间，胰岛素受体的减少不能仅用病毒诱导的大分子合成关闭来解释。此外，像脑心肌炎病毒这样不会在质膜中插入新抗原的病毒，不会引起胰岛素受体数量的变化。最可能的解释是病毒诱导的质膜变化改变或取代了胰岛素受体。结论是胰岛素受体测定是研究病毒感染对细胞膜影响的一种灵敏且定量的方法。这些数据还表明，与某些病毒感染相关的葡萄糖代谢异常可能部分归因于胰岛素受体浓度的变化。
