Advanced Glycation End Products: New Clinical and Molecular Perspectives

Abstract

Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.

The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases

“…Despite the achievements of the current analytical methods for measuring AGEs and sRAGE, there are still questions about their cost, complexity, and the variability of their results. There is a need for more standardized, noninvasive techniques with simpler applications and improved dependability [ 15 ].…”

“…The components of a mixture formed by the interaction of the used substances and chromatography columns can be analyzed by HPLC, which can identify the amounts of AGEs based on the intensity of their fluorescence. HPLC also enables a quicker investigation of protein-bound AGEs while determining their effect on the biologic properties of tissues [ 15 ]. Using MS, chemical compounds may be identified, characterized, and quantified based on fragmentation patterns.…”

“…Although the precise mechanisms of action of AGEs are unknown, they are most likely the outcome of the interaction with their membrane-bound receptor (RAGE) [ 12 , 13 , 14 ]. The AGE-RAGE complex ( Figure 1 ) can specifically activate the p21 protein, stimulating other signaling pathways such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and mitogen-activated protein kinase (MAP), as well as Janus kinase 1 and 2/Signal transducer and activators of transcription (JAK1&2/STAT1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which generate directly and indirectly reactive oxygen species (ROS) [ 15 ]. The activation of transcription factors such as nuclear factor kappa B (NF-kB) and the interferon-sensitive response element (ISRE) results in the production of interleukins, pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), and vascular cell adhesion molecule-1 (VCAM-1), contributing to inflammation and endothelial dysfunction, leading to the progression of chronic illness [ 15 , 16 , 17 , 18 , 19 ].…”

Advanced Glycation End Products in the Skin: Molecular Mechanisms, Methods of Measurement, and Inhibitory Pathways

“…The fluorescence level of AGEs in the skin has been shown to determine the survival rate of patients on dialysis ( 37 , 38 ), is an important marker of cardiovascular mortality in patients with chronic kidney disease (CKD) ( 38 , 39 ), and has been used to measure the risk of DM complications ( 40 ). The content of AGEs in the skin of haemodialysis patients is significantly higher than that of healthy individuals ( 33 , 41 ).…”

Pancreatic Stellate Cells and Metabolic Alteration: Physiology and Pathophysiology

“…Advanced glycation end products (AGEs) are formed by non-enzymatic glycation and oxidation of proteins or lipids. Increased AGE formation is observed in various pathogenic conditions with elevated glucose levels, such as DM ( Salazar et al, 2021 ). AGEs are recognized by the cell-surface receptor, receptor for advanced glycation end products (RAGE), which alters cellular functions.…”