The effect of Hyperglycemia and Oxidative Stress on the Development and Progress of Vascular Complications in Type 2 Diabetes

Abstract

The effect of Hyperglycemia and Oxidative Stress on the Development and Progress of Vascular Complications in Type 2 Diabetes Oxidative stress is the result of increased production of free radicals, which impair the cell function and cause many pathological conditions and diseases. The development of diabetes, its course and complications are closely associated with an imbalance in pro-antioxidative cell state and change of redox potential. Prolonged exposure to hyperglycemia is currently considered the major factor of the pathogenesis of atherosclerosis in diabetes. Atherosclerosis is the cause of about 80% of mortality in diabetics, and over 75% of all hospitalized diabetic patients have associated cardiovascular complications. Hyperglycemia induces different vascular tissue damage at the cellular level, which potentially accelerates the atherosclerotic processes. The most significant mechanisms responsible for acceleration of atherosclerotic processes in diabetic patients are: a) non-enzymatic protein and lipid glycosylation which interferes with normal function, in the way that it deranges molecular conformation, impairs enzymatic function, reduces the capacity of breakdown and interferes with recognition of protein structures by receptors; b) interaction of glycosylated proteins with their receptors resulting in induction of oxidative stress and pro-inflammatory reactions; c) polyol pathway; d) hexosamine pathway and e) activation of protein kinase C and impaired growth factor expression.

Glycans as Biomarkers: Status and Perspectives

“…1 % of the translated genome participates in oligosaccharide synthesis and function. Dynamic structural alterations of oligosaccharide chains have been implicated in a va riety of diseases, and they reflect a reprogramming of these complex control mechanisms, at early, inter me diate and mainly late glycoprotein processing steps (5,11).…”

“…Increased sialylation is found on both N-linked and O-linked glycoconjugates (11,(24)(25)(26). For instance, mucin production and secretion which is elevated in cancer cells, predominantly comprises sialomucin (generally undersulfated).…”

“…Fucosylation is significantly altered in cancer (11,(27)(28)(29). It may be related to greater branching of oligosaccharide chains, as well as changes (decrease or increase) in fucosyltransferase (FucT) activity.…”

“…As for galactosyltransferase (GalT) activity, this is elevated in bladder cancer and liver metastasis but decreased in hepatoma (11,30,31). Specifically, the activity, size, glycosylation and secretion of b4-GalT are all altered in cancer, i.e, decreased in colon and increased in lung, cervical and parotid gland cancer.…”

“…Profound changes in the expression and structure of carbohydrate components, resulting from rear -rangements of glycan biosynthetic pathways in the Golgi apparatus (19)(20)(21) or activation of particular onco genes (11,22) are hallmarks of all types of experimental and human cancers and are of special interest for their detection and prevention. A number of changes that occur are difficult to classify, but some generali zations can be deduced.…”