Sogujko Yu. R., Logash M. V., Sogujko R. R., Vilhova E.V.

THE BASIC MOLECULAR MECHANISMS OF DIABETIC COMPLICATIONS

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About the author:	Sogujko Yu. R., Logash M. V., Sogujko R. R., Vilhova E.V.
Heading	LITERATURE REVIEWS
Type of article	Review article
Annotation	Microvascular pathology in patients with diabetes mellitus has the functional, as well, as structural, characteristics. The thickening of the basal membrane there is main structural sign of diabetic microvascular pathology, and the main functional deviations there were increasing of the capillary permeability, speed of the blood flow, viscosity and disturbance of thrombosis [5]. Relationship between structural and functional changes, as well, as determination of causes and consequences of the diabetic microvascular pathology, remains the subject of discussion. Along with general signs, microvascular pathology has set of features, which defined by structure and function of the tissue, which was injured. Clinically, diabetic microvascular pathology too often manifested as retinopathy, glomerular dysfunction and neuropathy. Nonproliferative diabetic retinopathy is associated to the loss of pericytes, microaneurysm formation, increasing of vascular permeability. These microvascular disorders can cause to formation of nonperfusion areas and ischemia areas. Increasing of the intraglomerular pressure and protein content of intercellular matrix in diabetic nephropathy causes thickening of the basement membrane, mesangial expansion and glomerular hypertrophy. These changes caused decreasing of the area of the glomerular filtration and promote development of glomerulosclerosis [3]. The etiology of diabetic complications remains not till the end found out and controversial, while no doubt the fact, that the development of the microvascular disorders depends from duration of the pathology, as well as from quality of glycemic control. The hyperglycemia, probably, damages tissues, causes acute (reversible), as well as cumulative (irreversible) changes in the stable macromolecules. In the early stages, the pathological changes within the vessels, probably, caused by the acute (reversible) changes, while the role of cumulative (irreversible) changes, caused by hyperglycemia, increasing with the duration of the pathology. Non-enzymatic joining of the glucose on to the protein in the beginning caused reversible, late irreversible metabolic changes. Accumulation of the early glycation product caused different changes within the vessels, includes the capture and the modification of the low density lipoproteins (LDL), which provokes the immune responding. The prevalence of the antibody in to the glycated LDL caused formation of the immune complex, which affects in to the secretion of the cytokines, activity of the coagulation, permeability of the vessels and the expression of the growth factors of the vessels. Besides, the glycated proteins can oxidize themselves, and generates free radicals, which enhances the process of non-enzymatic joining of the glucose on to the macromolecules and enhances the development of the vessels pathology. Early glycation products, which made from collagen, DNA or another long-life molecules, can subjected to irreversible changes by the chemical transformation on to the advanced glycation end products. This elements are stable, thus accumulates along whole life within the tissues and the walls of the vessels, and their level never back to normal, even after the normalization of the glucose level [10]. According to Brownlee [2], there were three main mechanisms of the pathological action of the AGE: 1) they breaks the signal’s transduction through the membrane of the cells, which initiated by the ligands on the matrix proteins; 2) they changes the level of the instant signals (cytokines and free radicals), which cooperates with the receptors of the cells and demonstrates different pathological effects; 3) glycolysation of the internal proteins of the cells and DNA can disturbs their function directly. Conclusion: Diabetes mellitus remains an actual problem of nowadays. A detailed study of the molecular mechanisms of diabetic complications allows to analyze the main pathogenic and pathomorphological changes in this pathology.
Tags	diabetes mellitus, microangiopathy, glucose
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Publication of the article	«World of Medicine and Biology» №2(50) 2 part 2015 year, 214-217 pages, index UDK 616.379.-008.64-06.[611-018.1:576.32/.36]