Department of Endocrinology, Hospital de São João, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Pólo das Ciências da Saúde, 3000-548 Coimbra, Portugal.
Int J Mol Sci. 2020 Jan 18;21(2):645. doi: 10.3390/ijms21020645.
A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal-regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.
糖尿病的一个主要特征是持续的高血糖水平（高血糖），导致内皮功能障碍。短暂或长期的高血糖会导致糖尿病血管病变，这是一种继发性的全身损伤。C 肽是胰岛素原在胰腺β细胞内被丝氨酸蛋白酶切割产生的产物，其分泌量与胰岛素相似。人 C 肽的生物学活性对于预防糖尿病神经病变、肾病和其他血管并发症至关重要。1 型糖尿病的主要特征是缺乏胰岛素和 C 肽，但在 2 型糖尿病的后期阶段也观察到β细胞逐渐丧失。C 肽在动物和糖尿病患者中具有多方面的作用，这是由于其激活了多种细胞信号通路，突出了 p38 丝裂原活化蛋白激酶和细胞外信号调节激酶 1/2、Akt，以及内皮一氧化氮的产生。最近的研究工作强调了 C 肽在预防和改善糖尿病以及器官特异性并发症中的作用。C 肽在微血管病变和血管病变中的作用是通过保护血管功能、预防内皮细胞死亡、微血管通透性、新生内膜形成和血管炎症来实现的。在糖尿病动物和人类的几种组织中，用生理剂量的 C 肽替代可以改善微血管血流，主要是在神经组织、心肌、骨骼肌和肾脏中。本文提出了对人胰岛素原 C 肽在血管病变保护中多种细胞信号通路的综述，讨论了超越糖尿病神经病变和肾病治疗方法的最新进展的方法。
