Academic literature on the topic 'Glycation mediated diabetic'

Protein glycation is the random, nonenzymatic reaction of sugar and protein induced by diabetes and ageing; this process is quite different from glycosylation mediated by the enzymatic reactions catalysed by glycosyltransferases. Schiff bases form advanced glycation end products (AGEs) via intermediates, such as Amadori compounds. Although these AGEs form various molecular species, only a few of their structures have been determined. AGEs bind to different AGE receptors on the cell membrane and transmit signals to the cell. Signal transduction via the receptor of AGEs produces reactive oxygen species in cells, and oxidative stress is responsible for the onset of diabetic complications. This chapter introduces the molecular mechanisms of disease onset due to oxidative stress, including reactive oxygen species, caused by AGEs generated by protein glycation in a hyperglycaemic environment.

Hyperglycemic conditions and disruptions to glucose-regulating pathways lead to increased formation of highly reactive aldehydes, methylglyoxal and glyoxal, which react with certain arginine and lysine residues in proteins to form advanced glycation end products (AGEs). These AGEs damage the integrity of the retinal vasculature predominantly through two mechanisms: non-receptor-mediated damage, which pertains to the interaction with extracellular matrix and its functional properties, and receptor-mediated damage through AGE interactions with their receptors (RAGE) on pericytes and Muller cells. Damage occurring between AGE and RAGE potentially generates reactive oxygen species, inflammatory cytokines, and growth factors. Both mechanisms result in increased permeability of endothelial tight junctions, and this increased permeability can lead to leaking and eventually ischemia. Once this ischemia becomes significant, neovascularization can occur, the hallmark of proliferative diabetic retinopathy. Current pharmaceutical studies have shown the potential of AGE inhibitors, such as aminoguanidine, in decreasing AGE production, thus minimizing its effects in hyperglycemic conditions. Other pharmaceutical interventions, such as Tanshinone IIA, aim to protect cells from the impacts of AGEs. Future research will not only continue to understand the properties of AGEs and their effects on diabetes and diabetic complications like diabetic retinopathy but will also explore how they impact other diseases.

Hyperglycemia accelerates the formation of advanced glycation end products (AGEs). AGEs are a heterogeneous group of compounds generated by non-enzymatic glycation of proteins or lipids with glucose through Amadori rearrangement and its accumulation increases with aging in diabetes. AGEs augments ROS generation, diminishes the antioxidant defense of the cells, decreases mitochondrial membrane potential, ATP production, and elevates the levels of mitochondrial fission protein (Drp1) and mitophagic proteins (Parkin and PTEN) leading to dysfunction of mitochondria. In this chapter, we have discussed how AGEs trigger the endoplasmic reticulum stress and inflammation and mediate endothelial dysfunction in diabetes and also have discussed the role played by endogenous Paraoxonase 2 (PON2) in mitigating endothelial dysfunction by inhibiting the adverse effects of AGE.