Titov V N, Shiriaeva Iu K
Klin Lab Diagn. 2011 Nov(11):3-13.
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.
高血糖和糖尿病以及循环和结构蛋白的葡萄糖化学糖化(GLU)同时增加,是各种生理(GLU)代谢过程发生的条件:a)多元醇途径,细胞溶质中合成山梨醇,有机渗透剂产生细胞溶质高渗;GLU转化的半乳糖胺途径导致氨基糖毒素的形成;己糖转化为丙糖的强化导致细胞间介质中乙二醛和甲基乙二醛糖毒素的合成和积累增加。蛋白质糖基化反应与高血糖血症的程度和持续时间成比例,导致席夫碱、阿马多里产物和糖基化终产物的顺序形成。蛋白质与糖毒素的糖基化导致糖基化终产物的立即形成。内环境生物学功能的紊乱是由细胞间介质中GLU的积累决定的,GLU实际上是分子量较小的生物“废物”;而糖基化终产物则成为更大的生物“废物”。GLU代谢紊乱导致肌肉型小动脉、后小动脉、毛细血管和小静脉壁——循环系统微循环成分的血管——发生破坏性炎症过程,并在各种内脏器官中发展为糖尿病微血管病变。内皮厚度增加使小动脉和毛细血管腔变窄,增强了对血流的外周阻力。糖毒素作为双功能试剂在乳晕组织的胶原纤维中形成交联,增强血管壁硬度、周细胞功能障碍,并增加脉搏波传导速度。组织固定的糖基化终产物——大的内源性致炎物质,只有在细胞外蛋白水解、O2活性形式激活氧化以及炎症生物反应——巨噬细胞(功能性吞噬细胞)吞噬作用的情况下,才能在体内被利用。多余的GLU可以通过排泄生物反应清除。细胞外蛋白水解形成糖基化终产物的可溶性片段,这些片段在细胞间介质中与巨噬细胞受体的可溶性片段结合。在糖尿病情况下,监测血浆中GLU以及乙二醛、甲基乙二醛和丙二醛等糖毒素的含量是合理的。