The Significance of Oxidized Low-Density Lipoproteins and Receptors LOX-1 in Type 2 Diabetes Mellitus

INTRODUCTION. Type 2 diabetes mellitus (T2DM) occurs in 8.5% of the adult population with a tendency to increase. A characteristic feature of T2DM is dyslipidemia. One of its manifestations includes accumulation of increased concentration of oxidized low-density lipoproteins (ox-LDL) in circulation. Ox-LDL molecules act on cells through LOX-1 receptors.

THE PURPOSE OF THE REVIEW is to demonstrate results of studies presented in publications of 2010–2024 (PubMed, RSCI) indicating the pathogenetic role of ox-LDL and its LOX-1 receptors in T2DM development and course.

MATERIALS AND METHODS. In the analysis of more than 2800 literature sources (PubMed), in which together with term “­diabetes mellitus” keywords are found: ox-LDL (1150 sources) or LOX-1 (159 sources), as well as OLR1 (106 sources), 50 sources were identified that are directly related to T2DM and the studied functionally related markers — the LOX-1 receptor and its ligand ox-LDL.

RESULTS. LOX-1 is scavenger receptor that uses ox-LDL as its proper ligand. Gene OLR1 encodes ox-LDL receptor, LOX-1. The linking of T2DM and circulating levels of ox-LDL is bidirectional. The emerging insulin resistance directly correlates with oxidation of low-density lipoproteins, which is observed in more than 80% of patients and depends on the duration of T2DM. High plasma ligand levels are associated with increased type 2 diabetes risk. The mechanism of this association is thought to be related to functionally significant expression of LOX-1 on pancreatic cells. It was shown that pancreatic β-cells in the presence of ox-LDL increased production of the inducible early repressor of the cAMP signaling pathway, ICER. As result of ICER action, insulin production and secretion ceased. Increased ox-LDL concentrations are a pathogenetically significant factor in the development of atherosclerotic vascular lesions, as they stimulate the generation of foam cells. Ox-LDL-LOX-1-mediated interactions on the vascular surface led to endothelial dysfunction with subsequent development of tissue hypoperfusion and organ dysfunction.

CONCLUSION. Circulating ox-LDL, in interaction with its receptor LOX-1, makes a significant contribution to the development of T2DM, promoting its progression. Increased concentration of ox-LDL in blood increases the risk of severe T2DM, leading to endothelial dysfunction and promoting the development of atherosclerotic vascular lesions.

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