C 肽是胰岛素合成的副产品，被认为具有生物惰性，正在成为一种多功能分子。 C 肽在 1 型糖尿病 (T1DM) 和早期 T2DM 中具有抗炎和抗动脉粥样硬化作用。 C 肽通过激活 AMP 激活的蛋白激酶 α 来保护内皮细胞，从而抑制 NAD(P)H 氧化酶的活性并减少活性氧 (ROS) 的产生。它还通过调节高血糖诱导的 p53 上调和线粒体接头 p66shc 过度激活，以及降低 caspase-3 活性和促进 B 细胞淋巴瘤-2 的表达来防止细胞凋亡。此外，C 肽还可抑制血小板衍生生长因子 (PDGF)-β 受体和 p44/p42 丝裂原激活蛋白 (MAP) 激酶磷酸化，从而抑制血管平滑肌细胞 (VSMC) 增殖。它还能够消除核因子 kappa B (NF-kB) 信号传导（一种主要的促炎级联反应），从而减少白细胞粘附。因此，预计在 T1DM 中补充 C 肽可能会改善甚至预防终末器官损伤。与此形成鲜明对比的是，C 肽通过磷酸肌醇 3 激酶（PI-3 激酶）介导的途径增加单核细胞的募集和迁移，通过过氧化物酶体增殖物激活受体 γ 上调诱导脂质积累，并通过 Src- 刺激 VSMC 增殖和 CD4 淋巴细胞迁移。激酶和 PI-3K 依赖性途径。因此，它会促进晚期 T2DM 的动脉粥样硬化和微血管损伤。事实上，C 肽现在被认为是 T2DM 胰岛素抵抗的潜在生物标志物，并且与冠状动脉疾病风险增加有关。对糖尿病病理生理学的理解从单一激素缺乏转变为双激素紊乱，需要仔细考虑 C 肽作为一种独特分子的作用，具有广阔的诊断、预后和治疗应用前景。© 2024 Wiley periodicals有限责任公司。

C-peptide, a byproduct of insulin synthesis believed to be biologically inert, is emerging as a multifunctional molecule. C-peptide serves an anti-inflammatory and anti-atherogenic role in type 1 diabetes mellitus (T1DM) and early T2DM. C-peptide protects endothelial cells by activating AMP-activated protein kinase α, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species (ROS) generation. It also prevents apoptosis by regulating hyperglycemia-induced p53 upregulation and mitochondrial adaptor p66shc overactivation, as well as reducing caspase-3 activity and promoting expression of B-cell lymphoma-2. Additionally, C-peptide suppresses platelet-derived growth factor (PDGF)-beta receptor and p44/p42 mitogen-activated protein (MAP) kinase phosphorylation to inhibit vascular smooth muscle cells (VSMC) proliferation. It also diminishes leukocyte adhesion by virtue of its capacity to abolish nuclear factor kappa B (NF-kB) signaling, a major pro-inflammatory cascade. Consequently, it is envisaged that supplementation of C-peptide in T1DM might ameliorate or even prevent end-organ damage. In marked contrast, C-peptide increases monocyte recruitment and migration through phosphoinositide 3-kinase (PI-3 kinase)-mediated pathways, induces lipid accumulation via peroxisome proliferator-activated receptor γ upregulation, and stimulates VSMC proliferation and CD4+ lymphocyte migration through Src-kinase and PI-3K dependent pathways. Thus, it promotes atherosclerosis and microvascular damage in late T2DM. Indeed, C-peptide is now contemplated as a potential biomarker for insulin resistance in T2DM and linked to increased coronary artery disease risk. This shift in the understanding of the pathophysiology of diabetes from being a single hormone deficiency to a dual hormone disorder warrants a careful consideration of the role of C-peptide as a unique molecule with promising diagnostic, prognostic, and therapeutic applications.© 2024 Wiley Periodicals LLC.