[The glucose, glycotoxins and glycation products: the involvement into pathogenesis of microangiopathies, arteriolosclerosis and atherosclerosis].
The hyperglycemia and diabetes and the concurrent increase of glucose's chemical glycation of (GLU) circulating and structured proteins are the conditions of occurring of various a physiological (GLU) metabolism processes: a) a polyolic way with the synthesis in cells' cytosol of sorbitol alcohol, organic osmolit producing hyperosmolarity of cytosol; a galactosamine way of GLU transformation leads to aminoglycotoxins' formation; the intensification of hexose transformation into trioses leads to the increase of synthesis and accumulation of glycotoxins of glyoxal and methylglyoxal in intercellular medium. The reaction of proteins' glycation, proportionally to the magnitude and duration of hyperglycosemia, results in sequential formation of Shiff bases, Amadori products and glycation end products. The glycation of proteins with glycotoxins results in the immediate formation of glycation end products. The derangement of biologic function of endoecology is determined by the accumulation in the intercellular medium of GLU which factually is a biologic "refuses" with lesser molecular mass; and the glycation end products becomes greater biologic "refuses". The disorders of GLU metabolism results informing of destructive inflammatory processes in the wall of muscular type arterioles, postarterioles, capillaries and venules--the vessels of microcirculatory component of circulatory system with the development of diabetic microangiopathies in various internal organs. The increase of endothelium thickness narrows the lumen of arterioles and capillaries intensifying the peripheral resistance to blood flow. The glycotoxins as bi-functional reagents form the cross-links in collagen fibers of areolar tissue enhancing the hardness of vessels' walls, the pericytes' malfunction, and increasing the velocity of pulse wave conduction. The tissue fixed glycation end products--the large endogenous phlogogens can be utilized only in citu under the realization of extracellular proteolysis, the activation of oxidation by O2 active forms and the biologic reaction of inflammation--phagocytosis by macrophages, the functional phagocytes. The surplus of GLU can be removed by the biologic reaction of excretion. The extracellular proteolysis forms the soluble fragments of glycation end products which in the intercellular medium bind the soluble fragments of receptors of macrophages. Under diabetes, it is reasonable to monitor in blood plasma the content of both GLU and such glycotoxins as glyoxal, methylglyoxal and malonic dialdehyde.
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D050379:Arteriolosclerosis / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D003920:Diabetes Mellitus / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006037:Glyoxal / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways; D010084:Oxidation-Reduction; D059748:Proteolysis; D011765:Pyruvaldehyde / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism
D017127:Glycation End Products, Advanced; D018698:Glutamic Acid; D006037:Glyoxal; D011765:Pyruvaldehyde; D005947:Glucose