C-peptide in diabetes: A player in a dual hormone disorder?

Autor: Dakroub A; St. Francis Hospital and Heart Center, Roslyn, New York, USA., Dbouk A; Department of Medicine, Saint-Joseph University Medical School, Hotel-Dieu de France Hospital, Beirut, Lebanon., Asfour A; Leeds Teaching Hospitals NHS Trust, West Yorkshire, United Kingdom., Nasser SA; Keele University, Staffordshire, UK., El-Yazbi AF; Faculty of Pharmacy, Alamein International University (AIU), Alamein City, Egypt.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt., Sahebkar A; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran., Eid AA; Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon., Iratni R; Department of Biology, College of Science, United Arab Emirates University, Al Ain, UAE., Eid AH; Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2024 May; Vol. 239 (5), pp. e31212. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1002/jcp.31212
Abstrakt: 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.)
Databáze: MEDLINE
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