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      How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body?

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          Abstract

          The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs.

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          Most cited references51

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          Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking.

          Age-associated increases in collagen cross-linking and accumulation of advanced glycosylation products are both accelerated by diabetes, suggesting that glucose-derived cross-link formation may contribute to the development of chronic diabetic complications as well as certain physical changes of aging. Aminoguanidine, a nucleophilic hydrazine compound, prevented both the formation of fluorescent advanced nonenzymatic glycosylation products and the formation of glucose-derived collagen cross-links in vitro. Aminoguanidine administration to rats was equally effective in preventing diabetes-induced formation of fluorescent advanced nonenzymatic glycosylation products and cross-linking of arterial wall connective tissue protein in vivo. The identification of aminoguanidine as an inhibitor of advanced nonenzymatic glycosylation product formation now makes possible precise experimental definition of the pathogenetic significance of this process and suggests a potential clinical role for aminoguanidine in the future treatment of chronic diabetic complications.
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            Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy

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              Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1.

              The epidemics of insulin resistance (IR) and type 2 diabetes (T2D) affect the first world as well as less-developed countries, and now affect children as well. Persistently elevated oxidative stress and inflammation (OS/Infl) precede these polygenic conditions. A hallmark of contemporary lifestyle is a preference for thermally processed nutrients, replete with pro-OS/Infl advanced glycation endproducts (AGEs), which enhance appetite and cause overnutrition. We propose that chronic ingestion of oral AGEs promotes IR and T2D. The mechanism(s) involved in these findings were assessed in four generations of C57BL6 mice fed isocaloric diets with or without AGEs [synthetic methyl-glyoxal-derivatives (MG(+))]. F3/MG(+) mice manifested increased adiposity and premature IR, marked by severe deficiency of anti-AGE advanced glycation receptor 1 (AGER1) and of survival factor sirtuin 1 (SIRT1) in white adipose tissue (WAT), skeletal muscle, and liver. Impaired 2-deoxy-glucose uptake was associated with marked changes in insulin receptor (InsR), IRS-1, IRS-2, Akt activation, and a macrophage and adipocyte shift to a pro-OS/inflammatory (M1) phenotype. These features were absent in F3/MG(-) mice. MG stimulation of 3T3-L1 adipocytes led to suppressed AGER1 and SIRT1, and altered InsR, IRS-1, IRS-2 phosphorylation, and nuclear factor kappa-light chain enhancer of activated B cells (Nf-κB) p65 acetylation. Gene modulation revealed these effects to be coregulated by AGER1 and SIRT1. Thus, prolonged oral exposure to MG-AGEs can deplete host-defenses AGER1 and SIRT1, raise basal OS/Infl, and increase susceptibility to dysmetabolic IR. Because exposure to AGEs can be decreased, these insights provide an important framework for alleviating a major lifestyle-linked disease epidemic.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Foods
                Foods
                foods
                Foods
                MDPI
                2304-8158
                06 December 2016
                December 2016
                : 5
                : 4
                : 84
                Affiliations
                [1 ]University Lille, Inserm, CHU Lille, U995-LIRIC-Lille Inflammation Research International Center, F-59000 Lille, France; axel.guilbaud@ 123456gmail.com (A.G.); Eric.boulanger@ 123456univ-lille2.fr (E.B.)
                [2 ]UniLaSalle, EGEAL Unit, F-60026 Beauvais, France; Celine.Leridon@ 123456unilasalle.fr
                Author notes
                [* ]Correspondence: frederic.tessier@ 123456univ-lille2.fr ; Tel.: +33-3-20-62-35-61
                Article
                foods-05-00084
                10.3390/foods5040084
                5302422
                28231179
                942ea6a4-070e-4f84-a773-f41cbb93a38e
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 08 November 2016
                : 30 November 2016
                Categories
                Review

                glycation,maillard,advanced glycation end products,carboxymethyllysine,calorie restriction,fructose,probiotics,vitamins,diabetes,ageing

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