Kitabchi A E
Metabolism. 1977 May;26(5):547-87. doi: 10.1016/0026-0495(77)90099-3.
The recent work on proinsulin and C-peptide has been reviewed with major emphasis on the most significant findings since 1972. Proinsulin has now been established as the biosynthetic precursor of insulin in all species examined, including man, with a preproinsulin as a possible precursor of the prohormone. The conversion of proinsulin which appears to occur exclusively in the pancreas leads to equimolar production of insulin and C-peptide. Although proinsulin has a direct biologic effect which is one-tenth as much as that of insulin, C-peptide has no biologic activity on homologous or heterologous tissue and no ability to modify the action of insulin and/or proinsulin. Previous work on proinsulin immunoassay suggested that this prohormone, but not C-peptide, cross-reacts with insulin antiserum. On the other hand, in the C-peptide immunoassay, proinsulin but not insulin cross-reacts with the antiserum. Up to this time, therefore, it has not been possible to immunoassay human proinsulin or C-peptide specifically. The very recent work from the laboratory of Heding, however, has brought about major advances in this area in which human C-peptide and proinsulin can be separated in the plasma by the use of Sepharose particles. With this recent major advancement, it is now possible to measure human C-peptide specifically. This measurement has been shown to be a useful tool for the assessment of beta-cell function in diabetic patients treated with insulin and in insulinoma patients in whom endogenous C-peptide secretion is not suppressed with exogenous insulin-induced hypoglycemia. With the use of a specific enzyme which degrades insulin but not proinsulin, postprandial plasma proinsulin values have been measured in a large number of subjects under a variety of physiologic and pathologic conditions. These results, which are comparable to those obtained by the more laborious column chromatography, could be summarized as follows: (1) proinsulin values in lean, young normal subjects do not vary greatly in response to insulin secretagogues; (2) proinsulin secretion in response to glucose results in a greater percentage of proinsulin in the older age group than in the younger group; (3) in lean adult and juvenile diabetic patients, the percentage of proinsulin is not excessive, whereas obese diabetics and pregnant diabetics appear to secrete relatively greater proinsulin than their diabetic controls; and (4) whereas most hyperinsulinemic states (Cusing's syndrome, adult-onset diabetics, acromegaly, and glucocorticoid therapy) are not associated with an increase in percentage of proinsulin, hyperinsulinemia of insulinoma, selected cases of functional hypoglycemia, and genetic hyperproinsulinemia are associated with a greater percentage of proinsulin. Identification of a possible new proinsulin intermediate(s) in these conditions deserves further investigation...
近期有关胰岛素原和C肽的研究已被综述，重点关注了自1972年以来的最重要发现。现已确定，在包括人类在内的所有被研究物种中，胰岛素原是胰岛素的生物合成前体，而前胰岛素原可能是该激素原的前体。胰岛素原的转化似乎仅发生在胰腺中，会产生等摩尔量的胰岛素和C肽。尽管胰岛素原有直接的生物学效应，其强度为胰岛素的十分之一，但C肽对同源或异源组织没有生物学活性，也没有能力改变胰岛素和/或胰岛素原的作用。先前关于胰岛素原免疫测定的研究表明，这种激素原（而非C肽）与胰岛素抗血清发生交叉反应。另一方面，在C肽免疫测定中，胰岛素原（而非胰岛素）与抗血清发生交叉反应。因此，直到现在，还无法特异性地免疫测定人胰岛素原或C肽。然而，赫丁实验室最近的研究在这一领域取得了重大进展，通过使用琼脂糖颗粒可在血浆中分离人C肽和胰岛素原。随着这一最新的重大进展，现在能够特异性地测定人C肽。已证明这种测定对于评估接受胰岛素治疗的糖尿病患者以及内源性C肽分泌不会因外源性胰岛素诱导的低血糖而受到抑制的胰岛素瘤患者的β细胞功能是一种有用的工具。通过使用一种能降解胰岛素但不降解胰岛素原的特异性酶，已在大量受试者的各种生理和病理条件下测量了餐后血浆胰岛素原值。这些结果与通过更繁琐的柱色谱法获得的结果相当，可总结如下：（1）体型瘦、年轻的正常受试者的胰岛素原值对胰岛素促分泌剂的反应变化不大；（2）与年轻组相比，老年组中葡萄糖刺激的胰岛素原分泌导致胰岛素原的比例更高；（3）体型瘦的成年和青少年糖尿病患者的胰岛素原比例不过高，而肥胖糖尿病患者和妊娠糖尿病患者似乎比其糖尿病对照组分泌相对更多的胰岛素原；（4）虽然大多数高胰岛素血症状态（库欣综合征、成年发病型糖尿病、肢端肥大症和糖皮质激素治疗）与胰岛素原比例增加无关，但胰岛素瘤的高胰岛素血症、某些功能性低血糖病例和遗传性高胰岛素原血症与更高比例的胰岛素原有关。在这些情况下鉴定可能的新胰岛素原中间体值得进一步研究……
