RAGE receptor and its soluble isoforms in diabetes mellitus complications

Abstract

Chronic hyperglycemia, which is present in all types of diabetes, increases the formation of advanced glycation end-products (AGEs). The interaction of AGEs with receptor of advanced glycation end-products (RAGE) initiates a cascade of pro-inflammatory and pro-coagulant processes that result in oxidative stress, stimulating the formation and accumulation of more AGE molecules. This cyclic process, denominated metabolic memory, may explain the persistency of diabetic vascular complications in patients with satisfactory glycemic control. The RAGE found in several cell membranes is also present in soluble isoforms (esRAGE and cRAGE), which are generated by alternative deoxyribonucleic acid splicing or by proteolytic cleavage. This review focuses on new research into these mediators as potential biomarkers for vascular complications in diabetes.

A study of extracellular vesicle concentration in active diabetic Charcot neuroarthropathy

“…Plasma derived RAGE was recently considered as a possible biomarker for CN though the reported data are as yet inconclusive (Oliveira et al, 2013), and the underlying mechanisms were found to be subject to alteration of renal function (Semba et al, 2009). Recently, EVs have…”

Role of advanced glycation end products in the onset of diabetic kidney disease complications

“…Apart its transmembrane localization, RAGE structure consist of a soluble isoform (sRAGE), formed by two processes: alternative splicing (endogenous secretory receptor for AGE (esRAGE) or proteolytic cleavage (cRAGE) mediated by disintegrins and metalloproteinases. Studies suggest that sRAGE are risk predictors for vascular complications and therapeutic targets for the prevention of DM complications 38,39 . Quantification of glycation products is routinely analyzed through the measurement of glycated hemoglobin (HbA1c), which is used to assess metabolic control in diabetic patients 8 .…”

“…Microvascular complications of T1DM and T2DM appear to be related to genetic susceptibility, as there are individuals who have the disease for a long time and never developed nephropathy or retinopathy and individuals with the same glycemic control who develop microvascular complications. Also, the risk of diabetic nephropathy development increase in individuals who have relatives with T1DM with diabetic nephropathy 38,39 . Thus, genetic susceptibility may affect the development of complications.…”

“…Among the metabolic factors, hyperglycemia is the major determinant in the onset and progression of diabetic nephropathy 19,39 . Renal mesangial cells activated by AGEs induce excess extracellular matrix, which would explain the structural changes in the glomerulus, such as, mesangial expansion that occurs in diabetes and other renal diseases 18,30 .…”

Hiperglicemia induz hiperalgesia mecânica e despolarização do potencial de repouso da membrana de neurônios nociceptivos primários: papel dos canais de potássio sensíveis ao ATP

“…NADH inibe gliceraldeído-3-fosfato-desidrogenase, aumentando as concentrações de trioses fosfato, que formam um precursor intracelular de AGEs e que leva a formação de diacilglicerol e consequente ativação da proteína cinase C (PKC), que leva a indução ou inibe a expressão de vários genes na célula (OLIVEIRA et al, 2013).…”