Kobayashi M, Sasaoka T, Takata Y, Hisatomi A, Shigeta Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Diabetes. 1988 May;37(5):653-6. doi: 10.2337/diab.37.5.653.
Two sisters presented with severe insulin resistance and markedly decreased insulin binding to erythrocytes, cultured fibroblasts, and transformed lymphocytes. The dose-response curve of insulin-stimulated amino acid uptake in the fibroblasts was shifted to the right. The molecular weight of the insulin receptor on the transformed lymphocytes from the patients was 210,000 and could not be dissociated to alpha- and beta-subunits by dithiothreitol treatment. However, the proreceptor was cleaved by trypsin, and this led to production of a 135,000-Mr alpha-subunit. Insulin binding to the trypsin-treated cells increased to the normal level, and insulin action was normalized. These results suggest that the failure of proreceptor cleavage produces hormone-resistant states and that a proreceptor syndrome may be a unique disease entity for hormone resistance.
两名姐妹出现严重胰岛素抵抗，胰岛素与红细胞、培养的成纤维细胞及转化淋巴细胞的结合显著减少。成纤维细胞中胰岛素刺激氨基酸摄取的剂量反应曲线右移。患者转化淋巴细胞上胰岛素受体的分子量为210,000，经二硫苏糖醇处理后不能解离为α和β亚基。然而，前受体可被胰蛋白酶裂解，这导致产生一个分子量为135,000的α亚基。胰岛素与经胰蛋白酶处理的细胞的结合增加至正常水平，胰岛素作用也恢复正常。这些结果表明，前受体裂解失败会导致激素抵抗状态，前受体综合征可能是激素抵抗的一种独特疾病实体。
