C-peptide in diabetes: A player in a dual hormone disorder?
Author | Dakroub, Ali |
Author | Dbouk, Ali |
Author | Asfour, Aref |
Author | Nasser, Suzanne A. |
Author | El-Yazbi, Ahmed F. |
Author | Sahebkar, Amirhossein |
Author | Eid, Assaad A. |
Author | Iratni, Rabah |
Author | Eid, Ali H. |
Available date | 2024-05-09T11:06:00Z |
Publication Date | 2024-02-03 |
Publication Name | Journal of Cellular Physiology |
Identifier | http://dx.doi.org/10.1002/jcp.31212 |
Citation | Dakroub, A., Dbouk, A., Asfour, A., Nasser, S. A., El‐Yazbi, A. F., Sahebkar, A., ... & Eid, A. H. (2024). C‐peptide in diabetes: A player in a dual hormone disorder?. Journal of cellular physiology. |
ISSN | 0021-9541 |
ISSN | 1097-4652 |
Abstract | 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. |
Language | en |
Publisher | Wiley-Blackwell |
Subject | atherosclerosis cardiovascular disease insulin resistance metabolic disease vascular smooth muscle |
Type | Article |
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