Cohen R M, Given B D, Licinio-Paixao J, Provow S A, Rue P A, Frank B H, Root M A, Polonsky K S, Tager H S, Rubenstein A H
Metabolism. 1986 Dec;35(12):1137-46. doi: 10.1016/0026-0495(86)90027-2.
Two new radioimmunoassays for human proinsulin (hPI) have been developed and used to study patients with islet cell tumors and familial hyperproinsulinemia. Both antisera were adsorbed against human C-peptide conjugated to Sepharose, following which cross-reactivity to insulin and C-peptide was less than 0.001%. Antiserum 18D recognized the junction between the insulin B-chain and C-peptide and provided fivefold greater sensitivity than our previously reported hPI assay. Antiserum 11E recognized a determinant which includes or is adjacent to the A-chain-C-peptide junction or which is specified by the tertiary structure. In all 20 patients studied with surgically confirmed islet cell tumors, fasting plasma proinsulinlike material (PLM) was abnormal (greater than 3 SD from the mean measured in either lean or obese subjects) in both assays. This provided better discrimination than has been reported for PLM measured by gel filtration (abnormal in 13 of 14 of the present samples) with a considerably less laborious procedure. Samples from two families in which a mutant proinsulin is present in the circulation have immunoreactivity in the two assays consistent with previous identification of the molecule as an A-chain-C-peptide-linked intermediate of proinsulin conversion. The immunoreactivity of a sample from another family in which large amounts of proinsulin circulate are consistent with an intact molecule being the predominant form. This assay will be useful for confirming the diagnosis of insulin-secreting tumor in patients suspected of recurrent fasting hypoglycemia and in physiologic studies of proinsulin secretion.
已开发出两种用于检测人胰岛素原（hPI）的新型放射免疫分析方法，并用于研究胰岛细胞瘤和家族性高胰岛素原血症患者。两种抗血清均用与琼脂糖偶联的人C肽进行吸附，之后与胰岛素和C肽的交叉反应率均小于0.001%。抗血清18D识别胰岛素B链与C肽之间的连接点，其灵敏度比我们之前报道的hPI分析方法高五倍。抗血清11E识别一个决定簇，该决定簇包括A链-C肽连接点或与之相邻，或者由三级结构决定。在所有20例经手术确诊为胰岛细胞瘤的患者中，两种分析方法测得的空腹血浆胰岛素原样物质（PLM）均异常（比瘦人或肥胖受试者的平均测量值高出3个标准差以上）。与通过凝胶过滤法测量PLM（本样本中14例中有13例异常）相比，这提供了更好的区分度，且操作程序要简便得多。来自两个家族的样本，其循环中存在突变胰岛素原，在这两种分析方法中的免疫反应性与之前将该分子鉴定为胰岛素原转化的A链-C肽连接中间体一致。来自另一个家族的样本，其循环中有大量胰岛素原，其免疫反应性与完整分子为主要形式一致。该分析方法将有助于确诊疑似复发性空腹低血糖患者的胰岛素分泌肿瘤，并用于胰岛素原分泌的生理学研究。
