Shoelson S, Haneda M, Blix P, Nanjo A, Sanke T, Inouye K, Steiner D, Rubenstein A, Tager H
Nature. 1983 Apr 7;302(5908):540-3. doi: 10.1038/302540a0.
We have previously identified a structurally abnormal insulin in the serum and pancreas of a middle-aged man with diabetes mellitus which arose from a leucine for phenylalanine substitution at position 24 or 25 of the insulin B chain; further analysis of the patient's leukocyte DNA showed that one of the patient's insulin alleles had undergone mutation resulting in loss of an MboII restriction site normally present in the human insulin gene. Two additional and unrelated patients with the same clinical syndrome have now been identified (ref. 4 and unpublished results). All of these patients showed hyperglycaemia typical of diabetes and with marked hyperinsulinaemia typical of insulin resistance, but all three show normal tolerance to exogenously administered insulin. As the opportunity of examining pancreatic tissue from patients suspected of secreting insulin variants is rare, we have developed a method combining HPLC and radioimmunoassay to identify insulin variants isolated from human sera. By this method we have shown that all three patients noted above secrete structurally variant and chemically distinct insulins. In correction of our original assignment, one is identified as [LeuB25]insulin.
我们之前在一名中年糖尿病男性患者的血清和胰腺中鉴定出一种结构异常的胰岛素，它是由胰岛素B链第24或25位的亮氨酸取代苯丙氨酸产生的；对该患者白细胞DNA的进一步分析表明，患者的一个胰岛素等位基因发生了突变，导致人胰岛素基因中正常存在的一个MboII限制性位点缺失。现已鉴定出另外两名患有相同临床综合征且无亲缘关系的患者（参考文献4及未发表的结果）。所有这些患者均表现出糖尿病典型的高血糖症以及胰岛素抵抗典型的明显高胰岛素血症，但这三名患者对外源性胰岛素均表现出正常耐受性。由于检查疑似分泌胰岛素变体患者的胰腺组织的机会很少，我们开发了一种结合高效液相色谱法（HPLC）和放射免疫测定法的方法，以鉴定从人血清中分离出的胰岛素变体。通过这种方法，我们表明上述三名患者均分泌结构变体且化学性质不同的胰岛素。纠正我们原来的鉴定结果后，其中一种被鉴定为[LeuB25]胰岛素。
