The dual effect of C‐peptide on cellular activation and atherosclerosis: Protective or not?

Abstract

C-peptide is a cleavage product of proinsulin that acts on different type of cells, such as blood and endothelial cells. C-peptide biological effects may be different in type 1 and type 2 diabetes. Besides, there are further evidence for a functional interaction between C-peptide and insulin. In this way, C-peptide has ambiguous effects, acting as an antithrombotic or thrombotic molecule, depending on the physiological environment and disease conditions. Moreover, C-peptide regulates interaction of leucocytes, erythrocytes, and platelets with the endothelium. The beneficial effects include stimulation of nitric oxide production with its subsequent release by platelets and endothelium, the interaction with erythrocytes leading to the generation of adenosine triphosphate, and inhibition of atherogenic cytokine release. The undesirable action of C-peptide includes the chemotaxis of monocytes, lymphocytes, and smooth muscle cells. Also, C-peptide was related with increased lipid deposits and elevated smooth muscle cells proliferation in the vessel wall, contributing to atherosclerosis. Purpose of this review is to explore these dual roles of C-peptide on the blood, contributing at one side to haemostasis and the other to atherosclerotic process.

Higher fasting C-peptide is associated with post-stroke depression: a multicenter prospective cohort study

“…Another reasonable explanation is that C-peptide indirectly contributes to depression through its role in promoting atherosclerosis. A previous study has demonstrated that the deposit C-peptide on intima layer of the vessels promotes infiltration of monocytes/macrophages and lymphocytes CD4+, with impacts on the atherogenesis process [ 33 – 35 ]. Cerebrovascular atherosclerosis causes arterial stenosis, which leading to hemodynamic disturbance as well as low perfusion.…”

The effect of C-peptide on diabetic nephropathy: A review of molecular mechanisms

“…Structural bridges between A and B chains of proinsulin molecule [20] Stimulates Na + -K + -ATPase expression/activity [25] Modulates eNOS and iNOS activities and thereby hemodynamic states [20,26] Induces intracellular signaling especially Ca 2+ -dependent pathways [20,26] Modulates gene transcription/expression [20] Modulates glucose metabolism [20] Effects on cell survival [10] Modulates thrombotic events [27,28] Modulates lipid metabolism [29-31] Table 1; known physiological functions of c-peptide (eNOS=endothelial nitric oxide synthase, iNOS=inducible nitric oxide synthase)…”

Association Between C-Peptide Level and Subclinical Myocardial Injury

“…Previous studies have shown the association between Cpeptide and cardiovascular disease (19). Michelle et al examined the effect of C-peptide on atherosclerosis and found that high C-peptide levels were related with increased lipid deposits and smooth muscle cell proliferation in the vessel wall, contributing to atherosclerosis (12). Antonio Cabrera de Leon et al found that elevated C-peptide was associated with the incidence of myocardial infarction and coronary artery disease in the general population (20).…”

“…It is known that C-peptide has been widely used as a biomarker of diabetes diagnosis in clinical practice. Observational studies have found the association between Cpeptide and cardiovascular diseases (12,13). High levels of Cpeptide could increase the risks of atherosclerosis and myocardial infarction (14,15).…”