Genetic variability in the RAGE gene: Possible implications for nutrigenetics, nutrigenomics, and understanding the susceptibility to diabetic complications

Kaňková, Kateřina; Šebeková, Katarı́na

doi:10.1002/mnfr.200500007

Cited by 14 publications

(18 citation statements)

References 89 publications

(68 reference statements)

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“…Both biomarkers have been positively associated with the risk of GDM or gestational hyperglycaemia [44,45]. In addition, it has been proposed that food-derived AGEs may interact with glycoxidation-related genes, in particular, the AGE receptor (AGER) gene, to determine risk of type 2 diabetes by activating the AGE receptor signal transduction pathway involved in the inflammatory response [46]. Haem iron in red meat might also contribute to the increased risk of GDM, because body iron overload has been postulated to promote insulin resistance and increase the risk of type 2 diabetes [47].…”

Section: Discussionmentioning

confidence: 99%

A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus

et al. 2006

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Aims/hypothesis The aim of this study was to prospectively examine whether dietary patterns are related to risk of gestational diabetes mellitus (GDM). Methods This prospective cohort study included 13,110 women who were free of cardiovascular disease, cancer, type 2 diabetes and history of GDM. Subjects completed a validated semi-quantitative food frequency questionnaire in 1991, and reported at least one singleton pregnancy between 1992 and 1998 in the Nurses_ Health Study II. Two major dietary patterns (i.e. Fprudent_ and FWestern_) were identified through factor analysis. The prudent pattern was characterised by a high intake of fruit, green leafy vegetables, poultry and fish, whereas the Western pattern was characterised by high intake of red meat, processed meat, refined grain products, sweets, French fries and pizza. Results We documented 758 incident cases of GDM. After adjustment for age, parity, pre-pregnancy BMI and other covariates, the relative risk (RR) of GDM, comparing the highest with the lowest quintile of the Western pattern scores, was 1.63 (95% CI 1.20-2.21; p trend =0.001), whereas the RR comparing the lowest with the highest quintile of the prudent pattern scores was 1.39 (95% CI 1.08-1.80; p trend =0.018). The RR for each increment of one serving/ day was 1.61 (95% CI 1.25-2.07) for red meat and 1.64 (95% CI 1.13-2.38) for processed meat. Conclusions/interpretation These findings suggest that prepregnancy dietary patterns may affect women_s risk of developing GDM. A diet high in red and processed meat was associated with a significantly elevated risk.

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Section: Discussionmentioning

confidence: 99%

A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus

et al. 2006

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“…Generally, aglycon is no more effective than its glycoside. Kankovµ and Sebekovµ [31] have pointed out that hyperglycemia might act through i) the mitochondrial respiratory chain; ii) NADPH oxidase activation and iii) formation of AGEs, to allow for increased production of ROS. In addition, glucose itself can auto-oxidize to form O 2 9 -, OH, and H 2 O 2 in the presence of transition metal ions (Fe 3+ , Cu 2+ ) [2,3,32], and subsequently accelerate the formation of AGEs.…”

Section: Effects Of Hg On Expression Of Rage: Inhibition Of Flavonoidsmentioning

confidence: 99%

Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells

Huang

et al. 2009

Molecular Nutrition Food Res

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Activation of circulating monocytes by hyperglycemia is bound to play a role in inflammatory and atherosclerosis. In this study, we examined whether flavonoids (catechin, EGCG, luteolin, quercetin, rutin) - phytochemicals that may possible belong to a new class of advanced glycation end products (AGEs) inhibitors - can attenuate high glucose (15 mmol/L, HG)-induced inflammation in human monocytes. Our results show that all flavonoids significantly inhibited HG-induced expression of proinflammatory genes and proteins, including TNF-alpha, interleukin-1beta (IL-1beta), and cyclooxygenase (COX)-2, at a concentration of 20 microM. Flavonoids also prevented oxidative stress in activated monocytes, as demonstrated by their inhibitory effects on intracellular reactive oxygen species (ROS) and N(epsilon)-(carboxymethyl)lysine formation caused by HG. These inhibitory effects may involve inhibition of nuclear factor-kappaB activation and may be supported by downregulation of the following: i) PKC-dependent NADPH oxidase pathway; ii) phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated protein kinase, and iii) mRNA expression of receptor of AGEs. In addition, we found for the first time that lower levels of Bcl-2 protein under HG conditions could be countered by the action of flavonoids. Our data suggest that, along with their antioxidant activities, flavonoids possess anti-inflammatory properties and might therefore have additional protective effects against glycotoxin-related inflammation.

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“…Therefore, multiple approaches to identify polymorphisms of the RAGE gene have been studied in relation to diabetic complications. While some polymorphisms correlate with insulin resistance and early-or late-onset of diabetic complications [105][106][107][108], none have so far pointed to the possibility that RAGE is the most important factor in the pathology of human diabetes. Although mutations deleting RAGE function may not be compatible with life and therefore not found in cohort studies, the fact that Rage −/− mice are viable and do not show an overt phenotype contradict this hypothesis or point to important differences between mice (kept in a sterile environment) and human diabetes.…”

Section: Open Questions and Future Perspectivesmentioning

confidence: 99%

Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications

2009

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The pattern recognition receptor or receptor for AGE (RAGE) is constitutionally expressed in a few cell types only. However in almost all cells studied so far it is induced by reactions known to initiate inflammation. Its biological activity seems to be mainly dependent on the presence of its various ligands, including AGE, S100-calcium binding protein/calgranulins, high-mobility group protein 1, amyloid-β-peptides and the family of β-sheet fibrils, all known to be elevated in chronic metabolic, malignant and inflammatory diseases. The RAGE pathway interacts with cytokine-, lipopolysaccharide-, oxidised LDL-and glucose-triggered cellular reactions by turning a short-lasting inflammatory response into a sustained change of cellular function driven by perpetuated activation of the proinflammatory transcription factor, nuclear factor kappa-B. RAGE-mediated persistent cell activation is of pivotal importance in various experimental and clinical settings, including diabetes and its complications, neurodegeneration, ageing, tumour growth, and autoimmune and infectious inflammatory disease. Due to RAGE's central role in maintaining perpetuated cell activation, various therapeutic attempts to block RAGE or its ligands are currently under investigation. Despite broad experimental evidence for the role of RAGE in chronic disease, knowledge of its physiological function is still missing, limiting predictions about safety of long-term inhibition of RAGE×ligand interaction in chronic diseases.

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Genetic variability in the RAGE gene: Possible implications for nutrigenetics, nutrigenomics, and understanding the susceptibility to diabetic complications

Cited by 14 publications

References 89 publications

A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus

A prospective study of dietary patterns, meat intake and the risk of gestational diabetes mellitus

Naturally occurring flavonoids attenuate high glucose‐induced expression of proinflammatory cytokines in human monocytic THP‐1 cells

Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications

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