Yosten Gina L C, Maric-Bilkan Christine, Luppi Patrizia, Wahren John
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri;
Division of Cardiovascular Sciences, Vascular Biology and Hypertension Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi;
Am J Physiol Endocrinol Metab. 2014 Dec 1;307(11):E955-68. doi: 10.1152/ajpendo.00130.2014. Epub 2014 Sep 23.
Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes.
连接肽，即C肽，是胰岛素原激素的产物，与胰岛素等摩尔量释放。曾经有人认为C肽在生物学上是惰性的，除了在胰岛素正确折叠中发挥作用外几乎没有生物学意义，但现在已知C肽能特异性结合多种组织的细胞膜，并启动对百日咳毒素敏感的特定细胞内信号级联反应。尽管现在很清楚C肽是一种生物活性分子，但关于该肽的生理意义仍存在争议。有趣的是，C肽似乎能逆转高血糖在某些组织（包括肾脏、周围神经和血管系统）中的有害作用。因此，C肽是治疗糖尿病相关长期并发症的潜在治疗剂。本综述探讨了C肽在正常和疾病状态下可能的生理相关作用，并讨论了该肽对感觉神经、肾脏和血管功能的影响。此外，我们强调了该肽的细胞内作用，并提出了确定C肽受体的新策略。最后，提出了一个关于C肽与糖尿病微血管并发症发生发展关系的假说。
