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Current Diabetes Reports
Published in: Current Diabetes Reports 10/2016

01-10-2016 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis

Authors: Sherman S. Leung, Josephine M. Forbes, Danielle J. Borg

Published in: Current Diabetes Reports | Issue 10/2016

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Abstract

The receptor for advanced glycation end products (RAGE) is a novel protein increasingly studied in the pathogenesis of type 1 diabetes (T1D). RAGE is expressed by several immune cell types, including T cells, antigen-presenting cells, endothelial cells, and the endocrine cells of the pancreatic islets. RAGE binds various ligands including advanced glycation end products (AGEs), high-mobility group box protein 1 (HMGB1), S100 proteins, β-amyloid, β-sheet fibrils, and lipopolysaccharide. AGEs are a particularly interesting ligand because their exogenous introduction into the body can be accelerated by the consumption of AGE-rich processed foods. This review will detail RAGE isoforms and its ligands and discuss how RAGE binding on the aforementioned cells could be linked to T1D pathogenesis.
Literature
1.
Vissing H, Aagaard L, Tommerup N, Boel E. Localization of the human gene for advanced glycosylation end product-specific receptor (AGER) to chromosome 6p21.3. Genomics. 1994;24:606–8.PubMedCrossRef
2.
Forbes JM, Soderlund J, Yap FY, Knip M, Andrikopoulos S, Ilonen J, et al. Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes. Diabetologia. 2011;54:1032–42.PubMedCrossRef
3.
4.
Xue J, Rai V, Singer D, Chabierski S, Xie J, Reverdatto S, et al. Advanced glycation end product recognition by the receptor for AGEs. Structure. 2011;19:722–32.PubMedPubMedCentralCrossRef
5.
Hori O, Brett J, Slattery T, Cao R, Zhang J, Chen JX, et al. The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J Biol Chem. 1995;270:25752–61.PubMedCrossRef
6.
Yamamoto Y, Harashima A, Saito H, Tsuneyama K, Munesue S, Motoyoshi S, et al. Septic shock is associated with receptor for advanced glycation end products ligation of LPS. J Immunol. 2011;186:3248–57.PubMedCrossRef
7.
L. Wang, T. Chen, J. Wu, and Q. Huang. Lipopolysaccharide-induced inflammation is associated with receptor for advanced glycation end products in human endothelial cells (1096.5). FASEB J. 28. 2014.
8.
Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, et al. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell. 1999;97:889–901.PubMedCrossRef
9.
Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature. 1996;382:685–91.PubMedCrossRef
10.
Wilton R, Yousef MA, Saxena P, Szpunar M, Stevens FJ. Expression and purification of recombinant human receptor for advanced glycation endproducts in Escherichia coli. Protein Expr Purif. 2006;47:25–35.PubMedCrossRef
11.
12.
International Diabetes Federation. IDF diabetes atlas. 7th ed. Brussels: International Diabetes Federation; 2015.
13.
Todd JA, Bell JI, McDevitt HO. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987;329:599–604.PubMedCrossRef
14.
Lucassen AM, Julier C, Beressi JP, Boitard C, Froguel P, Lathrop M, et al. Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet. 1993;4:305–10.PubMedCrossRef
15.
Polychronakos C, Li Q. Understanding type 1 diabetes through genetics: advances and prospects. Nat Rev Genet. 2011;12:781–92.PubMedCrossRef
16.
Bakay M, Pandey R, Hakonarson H. Genes involved in type 1 diabetes: an update. Genes (Basel). 2013;4:499–521.
17.
Tishkoff SA, Verrelli BC. Patterns of human genetic diversity: implications for human evolutionary history and disease. Annu Rev Genomics Hum Genet. 2003;4:293–340.PubMedCrossRef
18.
Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986;314:1360–8.PubMedCrossRef
19.
Virk J, Li J, Vestergaard M, Obel C, Lu M, Olsen J. Early life disease programming during the preconception and prenatal period: making the link between stressful life events and type-1 diabetes. PLoS One. 2010;5, e11523.PubMedPubMedCentralCrossRef
20.
Podar T, Solntsev A, Karvonen M, Padaiga Z, Brigis G, Urbonaite B, et al. Increasing incidence of childhood-onset type I diabetes in 3 Baltic countries and Finland 1983-1998. Diabetologia. 2001;44 Suppl 3:B17–20.PubMedCrossRef
21.
W.-P. You and M. Henneberg, Type 1 diabetes prevalence increasing globally and regionally: the role of natural selection and life expectancy at birth. BMJ Open Diabetes Research & Care. 4. 2016.
22.
Oikarinen S, Martiskainen M, Tauriainen S, Huhtala H, Ilonen J, Veijola R, et al. Enterovirus RNA in blood is linked to the development of type 1 diabetes. Diabetes. 2011;60:276–9.PubMedCrossRef
23.
Lonnrot M, Korpela K, Knip M, Ilonen J, Simell O, Korhonen S, et al. Enterovirus infection as a risk factor for beta-cell autoimmunity in a prospectively observed birth cohort: the Finnish Diabetes Prediction and Prevention Study. Diabetes. 2000;49:1314–8.PubMedCrossRef
24.
Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattre P, et al. Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in beta cells. J Virol. 2000;74:10153–64.PubMedPubMedCentralCrossRef
25.
Horwitz MS, Bradley LM, Harbertson J, Krahl T, Lee J, Sarvetnick N. Diabetes induced by Coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med. 1998;4:781–5.PubMedCrossRef
26.
Akerblom HK, Virtanen SM, Ilonen J, Savilahti E, Vaarala O, Reunanen A, et al. Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study. Diabetologia. 2005;48:829–37.PubMedCrossRef
27.
Knip M, Akerblom HK, Becker D, Dosch HM, Dupre J, Fraser W, et al. Hydrolyzed infant formula and early beta-cell autoimmunity: a randomized clinical trial. JAMA. 2014;311:2279–87.PubMedPubMedCentralCrossRef
28.
Dong JY, Zhang WG, Chen JJ, Zhang ZL, Han SF, Qin LQ. Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies. Nutrients. 2013;5:3551–62.PubMedPubMedCentralCrossRef
29.
Martin T, Campbell RK. Vitamin D and diabetes. Diabetes Spectrum. 2011;24:113–8.CrossRef
30.
Norris JM, Yin X, Lamb MM, Barriga K, Seifert J, Hoffman M, et al. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA. 2007;298:1420–8.PubMedCrossRef
31.
Hindmarsh PC, Matthews DR, Di Silvio L, Kurtz AB, Brook CG. Relation between height velocity and fasting insulin concentrations. Arch Dis Child. 1988;63:665–6.PubMedPubMedCentralCrossRef
32.
Hypponen E, Kenward MG, Virtanen SM, Piitulainen A, Virta-Autio P, Tuomilehto J, et al. Infant feeding, early weight gain, and risk of type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes Care. 1999;22:1961–5.PubMedCrossRef
33.
Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, et al. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med. 2013;11:46.PubMedPubMedCentralCrossRef
34.
Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, et al. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One. 2011;6, e25792.PubMedPubMedCentralCrossRef
35.
Akirav EM, Preston-Hurlburt P, Garyu J, Henegariu O, Clynes R, Schmidt AM, et al. RAGE expression in human T cells: a link between environmental factors and adaptive immune responses. PLoS One. 2012;7, e34698.PubMedPubMedCentralCrossRef
36.
Han XQ, Gong ZJ, Xu SQ, Li X, Wang LK, Wu SM, et al. Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response. J Huazhong Univ Sci Technol Med Sci. 2014;34:10–7.PubMedCrossRef
37.
Wild CA, Bergmann C, Fritz G, Schuler P, Hoffmann TK, Lotfi R, et al. HMGB1 conveys immunosuppressive characteristics on regulatory and conventional T cells. Int Immunol. 2012;24:485–94.PubMedCrossRef
38.
Moser B, Janik S, Schiefer AI, Mullauer L, Bekos C, Scharrer A, et al. Expression of RAGE and HMGB1 in thymic epithelial tumors, thymic hyperplasia and regular thymic morphology. PLoS One. 2014;9, e94118.PubMedPubMedCentralCrossRef
39.
Pellat-Deceunynck C, Mellerin MP, Labarriere N, Jego G, Moreau-Aubry A, Harousseau JL, et al. The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells. Eur J Immunol. 2000;30:803–9.PubMedCrossRef
40.
Hama S, Takeichi O, Saito I, Ito K. Involvement of inducible nitric oxide synthase and receptor for advanced glycation end products in periapical granulomas. J Endod. 2007;33:137–41.PubMedCrossRef
41.
Miura J, Uchigata Y, Yamamoto Y, Takeuchi M, Sakurai S, Watanabe T, et al. AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes. J Diabetes Complicat. 2004;18:53–9.PubMedCrossRef
42.
Z. Li, M. J. Scott, E. K. Fan, Y. Li, J. Liu, G. Xiao, et al.. Tissue damage negatively regulates LPS-induced macrophage necroptosis. Cell Death Differ. 2016.
43.
Dumitriu IE, Baruah P, Valentinis B, Voll RE, Herrmann M, Nawroth PP, et al. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol. 2005;174:7506–15.PubMedCrossRef
44.
Buttari B, Profumo E, Facchiano F, Ozturk EI, Segoni L, Saso L, et al. Resveratrol prevents dendritic cell maturation in response to advanced glycation end products. Oxid Med Cell Longev. 2013;2013:574029.PubMedPubMedCentralCrossRef
45.
Dumitriu IE, Baruah P, Bianchi ME, Manfredi AA, Rovere-Querini P. Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells. Eur J Immunol. 2005;35:2184–90.PubMedCrossRef
46.
Parodi M, Pedrazzi M, Cantoni C, Averna M, Patrone M, Cavaletto M, et al. Natural killer (NK)/melanoma cell interaction induces NK-mediated release of chemotactic High Mobility Group Box-1 (HMGB1) capable of amplifying NK cell recruitment. Oncoimmunology. 2015;4, e1052353.PubMedPubMedCentralCrossRef
47.
Moser B, Desai DD, Downie MP, Chen Y, Yan SF, Herold K, et al. Receptor for advanced glycation end products expression on T cells contributes to antigen-specific cellular expansion in vivo. J Immunol. 2007;179:8051–8.PubMedCrossRef
48.
Loser K, Vogl T, Voskort M, Lueken A, Kupas V, Nacken W, et al. The Toll-like receptor 4 ligands Mrp8 and Mrp14 are crucial in the development of autoreactive CD8+ T cells. Nat Med. 2010;16:713–7.PubMedCrossRef
49.
Chen Y, Akirav EM, Chen W, Henegariu O, Moser B, Desai D, et al. RAGE ligation affects T cell activation and controls T cell differentiation. J Immunol. 2008;181:4272–8.PubMedPubMedCentralCrossRef
50.
Matsuoka N, Itoh T, Watarai H, Sekine-Kondo E, Nagata N, Okamoto K, et al. High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. J Clin Invest. 2010;120:735–43.PubMedPubMedCentralCrossRef
51.
Koyama M, Cheong M, Markey KA, Gartlan KH, Kuns RD, Locke KR, et al. Donor colonic CD103+ dendritic cells determine the severity of acute graft-versus-host disease. J Exp Med. 2015;212:1303–21.PubMedPubMedCentralCrossRef
52.
Narumi K, Miyakawa R, Ueda R, Hashimoto H, Yamamoto Y, Yoshida T, et al. Proinflammatory proteins S100A8/S100A9 activate NK cells via interaction with RAGE. J Immunol. 2015;194:5539–48.PubMedCrossRef
53.
Xu Y, Zhan Y, Lew AM, Naik SH, Kershaw MH. Differential development of murine dendritic cells by GM-CSF versus Flt3 ligand has implications for inflammation and trafficking. J Immunol. 2007;179:7577–84.PubMedCrossRef
54.
Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003;370:1097–109.PubMedPubMedCentralCrossRef
55.
Basta G, Lazzerini G, Massaro M, Simoncini T, Tanganelli P, Fu C, et al. Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation. 2002;105:816–22.PubMedCrossRef
56.
Guzman-Ruiz R, Ortega F, Rodriguez A, Vazquez-Martinez R, Diaz-Ruiz A, Garcia-Navarro S, et al. Alarmin high-mobility group B1 (HMGB1) is regulated in human adipocytes in insulin resistance and influences insulin secretion in beta-cells. Int J Obes (Lond). 2014;38:1545–54.CrossRef
57.
Han D, Yamamoto Y, Munesue S, Motoyoshi S, Saito H, Win MT, et al. Induction of receptor for advanced glycation end products by insufficient leptin action triggers pancreatic beta-cell failure in type 2 diabetes. Genes Cells. 2013;18:302–14.PubMedCrossRef
58.
Zhu Y, Shu T, Lin Y, Wang H, Yang J, Shi Y, et al. Inhibition of the receptor for advanced glycation endproducts (RAGE) protects pancreatic beta-cells. Biochem Biophys Res Commun. 2011;404:159–65.PubMedCrossRef
59.
Kaji Y, Usui T, Ishida S, Yamashiro K, Moore TC, Moore J, et al. Inhibition of diabetic leukostasis and blood-retinal barrier breakdown with a soluble form of a receptor for advanced glycation end products. Invest Ophthalmol Vis Sci. 2007;48:858–65.PubMedCrossRef
60.
Sun L, Sun C, Liang Z, Li H, Chen L, Luo H, et al. FSP1(+) fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells. Sci Rep. 2015;5:14871.PubMedPubMedCentralCrossRef
61.
62.
Lander HM, Tauras JM, Ogiste JS, Hori O, Moss RA, Schmidt AM. Activation of the receptor for advanced glycation end products triggers a p21(ras)-dependent mitogen-activated protein kinase pathway regulated by oxidant stress. J Biol Chem. 1997;272:17810–4.PubMedCrossRef
63.
Li J, Schmidt AM. Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products. J Biol Chem. 1997;272:16498–506.PubMedCrossRef
64.
Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, et al. Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors/binding proteins. J Biol Chem. 1994;269:9889–97.PubMed
65.
Harja E, Bu DX, Hudson BI, Chang JS, Shen X, Hallam K, et al. Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE−/− mice. J Clin Invest. 2008;118:183–94.PubMedCrossRef
66.
Guh JY, Huang JS, Chen HC, Hung WC, Lai YH, Chuang LY. Advanced glycation end product-induced proliferation in NRK-49F cells is dependent on the JAK2/STAT5 pathway and cyclin D1. Am J Kidney Dis. 2001;38:1096–104.PubMedCrossRef
67.
Hudson BI, Carter AM, Harja E, Kalea AZ, Arriero M, Yang H, et al. Identification, classification, and expression of RAGE gene splice variants. FASEB J. 2008;22:1572–80.PubMedCrossRef
68.
Kalea AZ, Reiniger N, Yang H, Arriero M, Schmidt AM, Hudson BI. Alternative splicing of the murine receptor for advanced glycation end-products (RAGE) gene. FASEB J. 2009;23:1766–74.PubMedPubMedCentralCrossRef
69.
Cheng A, Dong Y, Zhu F, Liu Y, Hou FF, Nie J. AGE-LDL activates Toll like receptor 4 pathway and promotes inflammatory cytokines production in renal tubular epithelial cells. Int J Biol Sci. 2013;9:94–107.PubMedPubMedCentralCrossRef
70.
Araki N, Higashi T, Mori T, Shibayama R, Kawabe Y, Kodama T, et al. Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction. Eur J Biochem. 1995;230:408–15.PubMedCrossRef
71.
Ohgami N, Nagai R, Ikemoto M, Arai H, Kuniyasu A, Horiuchi S, et al. Cd36, a member of the class b scavenger receptor family, as a receptor for advanced glycation end products. J Biol Chem. 2001;276:3195–202.PubMedCrossRef
72.
Pullerits R, Brisslert M, Jonsson IM, Tarkowski A. Soluble receptor for advanced glycation end products triggers a proinflammatory cytokine cascade via beta2 integrin Mac-1. Arthritis Rheum. 2006;54:3898–907.PubMedCrossRef
73.••
Salonen KM, Ryhanen SJ, Forbes JM, Harkonen T, Ilonen J, Laine AP, et al. Circulating concentrations of soluble receptor for AGE are associated with age and AGER gene polymorphisms in children with newly diagnosed type 1 diabetes. Diabetes Care. 2014;37:1975–81. This was the first study to demonstrate that a RAGE isoform associated with progression towards overt type 1 diabetes.PubMedCrossRef
74.
Salonen KM, Ryhanen SJ, Forbes JM, Borg DJ, Harkonen T, Ilonen J, et al. Decrease in circulating concentrations of soluble receptors for advanced glycation end products at the time of seroconversion to autoantibody positivity in children with prediabetes. Diabetes Care. 2015;38:665–70.PubMed
75.
Koschinsky T, He CJ, Mitsuhashi T, Bucala R, Liu C, Buenting C, et al. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci U S A. 1997;94:6474–9.PubMedPubMedCentralCrossRef
76.
Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2001;44:129–46.PubMedCrossRef
77.
Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, et al. Advanced glycation endproducts in food and their effects on health. Food Chem Toxicol. 2013;60:10–37.PubMedCrossRef
78.••
Beyan H, Riese H, Hawa MI, Beretta G, Davidson HW, Hutton JC, et al. Glycotoxin and autoantibodies are additive environmentally determined predictors of type 1 diabetes: a twin and population study. Diabetes. 2012;61:1192–8. This was the first study to demonstrate that RAGE ligands, AGEs, acted as independent predictors for type 1 diabetes progression in ICA+ children.PubMedPubMedCentralCrossRef
79.
Barat P, Cammas B, Lacoste A, Harambat J, Vautier V, Nacka F, et al. Advanced glycation end products in children with type 1 diabetes: family matters? Diabetes Care. 2012;35:e1.PubMedCrossRef
80.
Mericq V, Piccardo C, Cai W, Chen X, Zhu L, Striker GE, et al. Maternally transmitted and food-derived glycotoxins: a factor preconditioning the young to diabetes? Diabetes Care. 2010;33:2232–7.PubMedPubMedCentralCrossRef
81.
Coughlan MT, Yap FY, Tong DC, Andrikopoulos S, Gasser A, Thallas-Bonke V, et al. Advanced glycation end products are direct modulators of beta-cell function. Diabetes. 2011;60:2523–32.PubMedPubMedCentralCrossRef
82.
Peppa M, He C, Hattori M, McEvoy R, Zheng F, Vlassara H. Fetal or neonatal low-glycotoxin environment prevents autoimmune diabetes in NOD mice. Diabetes. 2003;52:1441–8.PubMedCrossRef
83.
Leslie RD, Beyan H, Sawtell P, Boehm BO, Spector TD, Snieder H. Level of an advanced glycated end product is genetically determined: a study of normal twins. Diabetes. 2003;52:2441–4.PubMedCrossRef
84.
Jaisson S, Gillery P. Evaluation of nonenzymatic posttranslational modification-derived products as biomarkers of molecular aging of proteins. Clin Chem. 2010;56:1401–12.PubMedCrossRef
85.
Doyle HA, Mamula MJ. Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol. 2001;22:443–9.PubMedCrossRef
86.
Delong T, Wiles TA, Baker RL, Bradley B, Barbour G, Reisdorph R, et al. Pathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion. Science. 2016;351:711–4.PubMedPubMedCentralCrossRef
87.
van Lummel M, Duinkerken G, van Veelen PA, de Ru A, Cordfunke R, Zaldumbide A, et al. Posttranslational modification of HLA-DQ binding islet autoantigens in type 1 diabetes. Diabetes. 2014;63:237–47.PubMedCrossRef
88.
McLaughlin RJ, Spindler MP, van Lummel M, Roep BO. Where, how, and when: positioning posttranslational modification within type 1 diabetes pathogenesis. Curr Diabetes Rep. 2016;16:1–9.CrossRef
89.
Abdel-Wahab YH, O’Harte FP, Boyd AC, Barnett CR, Flatt PR. Glycation of insulin results in reduced biological activity in mice. Acta Diabetol. 1997;34:265–70.PubMedCrossRef
90.
Abdel-Wahab YH, O’Harte FP, Ratcliff H, McClenaghan NH, Barnett CR, Flatt PR. Glycation of insulin in the islets of Langerhans of normal and diabetic animals. Diabetes. 1996;45:1489–96.PubMedCrossRef
91.
Hunter SJ, Boyd AC, O’Harte FP, McKillop AM, Wiggam MI, Mooney MH, et al. Demonstration of glycated insulin in human diabetic plasma and decreased biological activity assessed by euglycemic-hyperinsulinemic clamp technique in humans. Diabetes. 2003;52:492–8.PubMedCrossRef
92.
Oliveira LM, Lages A, Gomes RA, Neves H, Familia C, Coelho AV, et al. Insulin glycation by methylglyoxal results in native-like aggregation and inhibition of fibril formation. BMC Biochem. 2011;12:41.PubMedPubMedCentralCrossRef
93.
Vay D, Vidali M, Allochis G, Cusaro C, Rolla R, Mottaran E, et al. Antibodies against advanced glycation end product Nepsilon-(carboxymethyl)lysine in healthy controls and diabetic patients. Diabetologia. 2000;43:1385–8.PubMedCrossRef
94.
Turk Z, Ljubic S, Turk N, Benko B. Detection of autoantibodies against advanced glycation endproducts and AGE-immune complexes in serum of patients with diabetes mellitus. Clin Chim Acta. 2001;303:105–15.PubMedCrossRef
95.
Ahmad S, Moinuddin, Shahab U, Habib S, Salman Khan M, Alam K, et al. Glycoxidative damage to human DNA: neo-antigenic epitopes on DNA molecule could be a possible reason for autoimmune response in type 1 diabetes. Glycobiology. 2014;24:281–91.PubMedCrossRef
96.
Mir AR, Moinuddin. Glycoxidation of histone proteins in autoimmune disorders. Clin Chim Acta. 2015;450:25–30.PubMedCrossRef
97.
Chikazawa M, Otaki N, Shibata T, Miyashita H, Kawai Y, Maruyama S, et al. Multispecificity of immunoglobulin M antibodies raised against advanced glycation end products: involvement of electronegative potential of antigens. J Biol Chem. 2013;288:13204–14.PubMedPubMedCentralCrossRef
98.
Ligier S, Fortin PR, Newkirk MM. A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE. Rheumatology. 1998;37:1307–14.CrossRef
99.
Goodwin GH, Sanders C, Johns EW. A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem. 1973;38:14–9.PubMedCrossRef
100.
Penfold SA, Coughlan MT, Patel SK, Srivastava PM, Sourris KC, Steer D, et al. Circulating high-molecular-weight RAGE ligands activate pathways implicated in the development of diabetic nephropathy. Kidney Int. 2010;78:287–95.PubMedCrossRef
101.
Tian J, Avalos AM, Mao SY, Chen B, Senthil K, Wu H, et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol. 2007;8:487–96.PubMedCrossRef
102.
Yang X, Wang H, Zhang M, Liu J, Lv B, Chen F. HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-kappaB and cGMP dependent mechanisms. Diagn Pathol. 2015;10:134.PubMedPubMedCentralCrossRef
103.
Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, et al. Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J. 2003;22:5551–60.PubMedPubMedCentralCrossRef
104.
Degryse B, Bonaldi T, Scaffidi P, Muller S, Resnati M, Sanvito F, et al. The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. J Cell Biol. 2001;152:1197–206.PubMedPubMedCentralCrossRef
105.
Urbonaviciute V, Furnrohr BG, Meister S, Munoz L, Heyder P, De Marchis F, et al. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. 2008;205:3007–18.PubMedPubMedCentralCrossRef
106.
Han J, Zhong J, Wei W, Wang Y, Huang Y, Yang P, et al. Extracellular high-mobility group box 1 acts as an innate immune mediator to enhance autoimmune progression and diabetes onset in NOD mice. Diabetes. 2008;57:2118–27.PubMedPubMedCentralCrossRef
107.
108.
Schafer BW, Fritschy JM, Murmann P, Troxler H, Durussel I, Heizmann CW, et al. Brain S100A5 is a novel calcium-, zinc-, and copper ion-binding protein of the EF-hand superfamily. J Biol Chem. 2000;275:30623–30.PubMedCrossRef
109.
Leukert N, Vogl T, Strupat K, Reichelt R, Sorg C, Roth J. Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity. J Mol Biol. 2006;359:961–72.PubMedCrossRef
110.
Ostendorp T, Leclerc E, Galichet A, Koch M, Demling N, Weigle B, et al. Structural and functional insights into RAGE activation by multimeric S100B. EMBO J. 2007;26:3868–78.PubMedPubMedCentralCrossRef
111.
K. M. Wartchow, A. C. Tramontina, D. F. de Souza, R. Biasibetti, L. D. Bobermin, and C. A. Goncalves. Insulin stimulates S100B secretion and these proteins antagonistically modulate brain glucose metabolism. Neurochem Res. 2016.
112.
Rammes A, Roth J, Goebeler M, Klempt M, Hartmann M, Sorg C. Myeloid-related protein (MRP) 8 and MRP14, calcium-binding proteins of the S100 family, are secreted by activated monocytes via a novel, tubulin-dependent pathway. J Biol Chem. 1997;272:9496–502.PubMedCrossRef
113.
Tardif MR, Chapeton-Montes JA, Posvandzic A, Page N, Gilbert C, Tessier PA. Secretion of S100A8, S100A9, and S100A12 by neutrophils involves reactive oxygen species and potassium efflux. J Immunol Res. 2015;2015:296149.PubMedPubMedCentralCrossRef
114.
Passey RJ, Williams E, Lichanska AM, Wells C, Hu S, Geczy CL, et al. A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. J Immunol. 1999;163:2209–16.PubMed
115.
Hobbs JA, May R, Tanousis K, McNeill E, Mathies M, Gebhardt C, et al. Myeloid cell function in MRP-14 (S100A9) null mice. Mol Cell Biol. 2003;23:2564–76.PubMedPubMedCentralCrossRef
116.
Bouma G, Coppens JM, Lam-Tse WK, Luini W, Sintnicolaas K, Levering WH, et al. An increased MRP8/14 expression and adhesion, but a decreased migration towards proinflammatory chemokines of type 1 diabetes monocytes. Clin Exp Immunol. 2005;141:509–17.PubMedPubMedCentralCrossRef
117.
Bouma G, Lam-Tse WK, Wierenga-Wolf AF, Drexhage HA, Versnel MA. Increased serum levels of MRP-8/14 in type 1 diabetes induce an increased expression of CD11b and an enhanced adhesion of circulating monocytes to fibronectin. Diabetes. 2004;53:1979–86.PubMedCrossRef
118.
Ikemoto M, Matsumoto S, Egawa H, Okitsu T, Iwanaga Y, Umemoto S, et al. A case with transient increases in serum S100A8/A9 levels implying acute inflammatory responses after pancreatic islet transplantation. Ann Clin Biochem. 2007;44:570–2.PubMedCrossRef
119.
Xiong Z, O’Hanlon D, Becker LE, Roder J, MacDonald JF, Marks A. Enhanced calcium transients in glial cells in neonatal cerebellar cultures derived from S100B null mice. Exp Cell Res. 2000;257:281–9.PubMedCrossRef
120.
Winer S, Tsui H, Lau A, Song A, Li X, Cheung RK, et al. Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive. Nat Med. 2003;9:198–205.PubMedCrossRef
121.
Gomez-Tourino I, Simon-Vazquez R, Alonso-Lorenzo J, Arif S, Calvino-Sampedro C, Gonzalez-Fernandez A, et al. Characterization of the autoimmune response against the nerve tissue S100beta in patients with type 1 diabetes. Clin Exp Immunol. 2015;180:207–17.PubMedPubMedCentralCrossRef
122.
Lotosh NG, Savel’eva EK, Selishcheva AA, Savel’ev SV. Autoantibodies to neuron-specific proteins S100, GFAP, MBP and NGF in the serum of rats with streptozotocin-induced diabetes. Bull Exp Biol Med. 2013;155:48–51.PubMedCrossRef
123.
Serre L, Fazilleau N, Guerder S. Central tolerance spares the private high-avidity CD4(+) T-cell repertoire specific for an islet antigen in NOD mice. Eur J Immunol. 2015;45:1946–56.PubMedCrossRef
124.
Jin X, Yao T, Zhou Z, Zhu J, Zhang S, Hu W, et al. Advanced glycation end products enhance macrophages polarization into M1 phenotype through activating RAGE/NF-kappaB pathway. Biomed Res Int. 2015;2015:732450.PubMedPubMedCentral
125.
Yan SF, Ramasamy R, Schmidt AM. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Rev Endocrinol. 2008;4:285–93.
126.
Qin Q, Niu J, Wang Z, Xu W, Qiao Z, Gu Y. Heparanase induced by advanced glycation end products (AGEs) promotes macrophage migration involving RAGE and PI3K/AKT pathway. Cardiovasc Diabetol. 2013;12:37.PubMedPubMedCentralCrossRef
127.
Friggeri A, Banerjee S, Biswas S, de Freitas A, Liu G, Bierhaus A, et al. Participation of the receptor for advanced glycation end products in efferocytosis. J Immunol. 2011;186:6191–8.PubMedPubMedCentralCrossRef
128.
Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol. 2008;8:533–44.PubMedCrossRef
129.
Yui S, Sasaki T, Araki N, Horiuchi S, Yamazaki M. Induction of macrophage growth by advanced glycation end products of the Maillard reaction. J Immunol. 1994;152:1943–9.PubMed
130.
Tesch G, Sourris KC, Summers SA, McCarthy D, Ward MS, Borg DJ, et al. Deletion of bone-marrow-derived receptor for AGEs (RAGE) improves renal function in an experimental mouse model of diabetes. Diabetologia. 2014;57:1977–85.PubMedCrossRef
131.
Rojas A, Delgado-Lopez F, Perez-Castro R, Gonzalez I, Romero J, Rojas I, et al. HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism. Tumour Biol. 2016;37:3321–9.PubMedCrossRef
132.
Kang R, Chen R, Xie M, Cao L, Lotze MT, Tang D, et al. The receptor for advanced glycation end products activates the AIM2 inflammasome in acute pancreatitis. J Immunol. 2016;196:4331–7.PubMedCrossRef
133.
Fernandes-Alnemri T, Yu J-W, Datta P, Wu J, Alnemri ES. AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature. 2009;458:509–13.PubMedPubMedCentralCrossRef
134.
Lehuen A, Diana J, Zaccone P, Cooke A. Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol. 2010;10:501–13.PubMedCrossRef
135.
Flodström-Tullberg M, Yadav D, Hägerkvist R, Tsai D, Secrest P, Stotland A, et al. Target cell expression of suppressor of cytokine signaling-1 prevents diabetes in the NOD mouse. Diabetes. 2003;52:2696–700.PubMedCrossRef
136.
Chong MMW, Chen Y, Darwiche R, Dudek NL, Irawaty W, Santamaria P, et al. Suppressor of cytokine signaling-1 overexpression protects pancreatic β cells from CD8+ T cell-mediated autoimmune destruction. J Immunol. 2004;172:5714–21.PubMedCrossRef
137.
Rodacki M, Svoren B, Butty V, Besse W, Laffel L, Benoist C, et al. Altered natural killer cells in type 1 diabetic patients. Diabetes. 2007;56:177–85.PubMedCrossRef
138.
Brauner H, Elemans M, Lemos S, Broberger C, Holmberg D, Flodstrom-Tullberg M, et al. Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice. J Immunol. 2010;184:2272–80.PubMedCrossRef
139.
DeMarco RA, Fink MP, Lotze MT. Monocytes promote natural killer cell interferon gamma production in response to the endogenous danger signal HMGB1. Mol Immunol. 2005;42:433–44.PubMedCrossRef
140.
Sinha P, Okoro C, Foell D, Freeze HH, Ostrand-Rosenberg S, Srikrishna G. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol. 2008;181:4666–75.PubMedPubMedCentralCrossRef
141.
Ichikawa M, Williams R, Wang L, Vogl T, Srikrishna G. S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res. 2011;9:133–48.PubMedPubMedCentralCrossRef
142.
Cheng P, Corzo CA, Luetteke N, Yu B, Nagaraj S, Bui MM, et al. Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med. 2008;205:2235–49.PubMedPubMedCentralCrossRef
143.
Sade-Feldman M, Kanterman J, Ish-Shalom E, Elnekave M, Horwitz E, Baniyash M. Tumor necrosis factor-alpha blocks differentiation and enhances suppressive activity of immature myeloid cells during chronic inflammation. Immunity. 2013;38:541–54.PubMedCrossRef
144.
Sunahori K, Yamamura M, Yamana J, Takasugi K, Kawashima M, Yamamoto H, et al. The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis. Arthritis Res Ther. 2006;8:R69.PubMedPubMedCentralCrossRef
145.
Schelbergen RF, Blom AB, de Munter W, Vogl T, Roth J, van den Berg WB, et al. Alarmins s100a8 and s100a9 stimulate production of pro-inflammatory cytokines in M2 macrophages without changing their M2 membrane phenotype. Ann Rheum Dis. 2012;71:A76.CrossRef
146.
Matteucci E, Ghimenti M, Di Beo S, Giampietro O. Altered proportions of naïve, central memory and terminally differentiated central memory subsets among CD4+ and CD8+ T cells expressing CD26 in patients with type 1 diabetes. J Clin Immunol. 2011;31:977–84.PubMedCrossRef
147.
M. L. Bian, O. Haigh, D. Munster, M. Harris, A. Cotterill, J. J. Miles, et al.. Reactivated CD4+ Tm cells of T1D patients and siblings display an exaggerated effector phenotype with heightened sensitivity to activation-induced cell death. Diabetes. 2014.
148.•
Nagareddy PR, Murphy AJ, Stirzaker RA, Hu Y, Yu S, Miller RG, et al. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab. 2013;17:695–708. This study showed that the S100A8/A9 levels correlate with leukocyte counts in individuals with type 1 diabetes, and the interaction of S100A8/A9 and RAGE promote myelopoiesis in hyperglycaemic environments.PubMedPubMedCentralCrossRef
149.
Nagareddy PR, Kraakman M, Masters SL, Stirzaker RA, Gorman DJ, Grant RW, et al. Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metab. 2014;19:821–35.PubMedPubMedCentralCrossRef
150.
Reis C, Sousa E. Dendritic cells in a mature age. Nat Rev Immunol. 2006;6:476–83.CrossRef
151.
Heilmann M, Wellner A, Gadermaier G, Ilchmann A, Briza P, Krause M, et al. Ovalbumin modified with pyrraline, a Maillard reaction product, shows enhanced T-cell immunogenicity. J Biol Chem. 2014;289:7919–28.PubMedPubMedCentralCrossRef
152.
Ilchmann A, Burgdorf S, Scheurer S, Waibler Z, Nagai R, Wellner A, et al. Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: role of macrophage scavenger receptor class A type I and II. J Allergy Clin Immunol. 2010;125:175-83. e1–11.CrossRef
153.
Hilmenyuk T, Bellinghausen I, Heydenreich B, Ilchmann A, Toda M, Grabbe S, et al. Effects of glycation of the model food allergen ovalbumin on antigen uptake and presentation by human dendritic cells. Immunology. 2010;129:437–45.PubMedPubMedCentralCrossRef
154.
Kumar RK, Herbert C, Foster PS. The “classical” ovalbumin challenge model of asthma in mice. Curr Drug Targets. 2008;9:485–94.PubMedCrossRef
155.
Buttari B, Profumo E, Capozzi A, Facchiano F, Saso L, Sorice M, et al. Advanced glycation end products of human beta(2) glycoprotein I modulate the maturation and function of DCs. Blood. 2011;117:6152–61.PubMedCrossRef
156.
Price CL, Sharp PS, North ME, Rainbow SJ, Knight SC. Advanced glycation end products modulate the maturation and function of peripheral blood dendritic cells. Diabetes. 2004;53:1452–8.PubMedCrossRef
157.
158.
Pejnovic NN, Pantic JM, Jovanovic IP, Radosavljevic GD, Milovanovic MZ, Nikolic IG, et al. Galectin-3 deficiency accelerates high-fat diet-induced obesity and amplifies inflammation in adipose tissue and pancreatic islets. Diabetes. 2013;62:1932–44.PubMedPubMedCentralCrossRef
159.
Su Z, Sun C, Zhou C, Liu Y, Zhu H, Sandoghchian S, et al. HMGB1 blockade attenuates experimental autoimmune myocarditis and suppresses Th17-cell expansion. Eur J Immunol. 2011;41:3586–95.PubMedCrossRef
160.
Tang Q, Li J, Zhu H, Li P, Zou Z, Xiao Y. Hmgb1-IL-23-IL-17-IL-6-Stat3 axis promotes tumor growth in murine models of melanoma. Mediat Inflamm. 2013;2013:713859.
161.
Zhang LT, Yao YM, Yao FH, Huang LF, Dong N, Yu Y, et al. Association between high-mobility group box-1 protein release and immune function of dendritic cells in thermal injury. J Interferon Cytokine Res. 2010;30:487–95.PubMedCrossRef
162.•
Kim TS, Gorski SA, Hahn S, Murphy KM, Braciale TJ. Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8(+) T cell differentiation by a CD24-dependent mechanism. Immunity. 2014;40:400–13. This study showed that CD8+ T cell activation could be regulated via CD24 through HMGB1 engagement of T cell RAGE.PubMedPubMedCentralCrossRef
163.
Manfredi AA, Capobianco A, Esposito A, De Cobelli F, Canu T, Monno A, et al. Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes. J Immunol. 2008;180:2270–5.PubMedCrossRef
164.
Huber JP, Ramos HJ, Gill MA, Farrar JD. Cutting edge: type I IFN reverses human Th2 commitment and stability by suppressing GATA3. J Immunol. 2010;185:813–7.PubMedPubMedCentralCrossRef
165.
Duan L, Wang CY, Chen J, Gong Q, Zhu P, Zheng F, et al. High-mobility group box 1 promotes early acute allograft rejection by enhancing IL-6-dependent Th17 alloreactive response. Lab Invest. 2011;91:43–53.PubMedCrossRef
166.
Zhang Y, Yao YM, Huang LF, Dong N, Yu Y, Sheng ZY. The potential effect and mechanism of high-mobility group box 1 protein on regulatory T cell-mediated immunosuppression. J Interferon Cytokine Res. 2011;31:249–57.PubMedCrossRef
167.
Mu L, Zhang Y, Sun B, Wang J, Xie X, Li N, et al. Activation of the receptor for advanced glycation end products (RAGE) exacerbates experimental autoimmune myasthenia gravis symptoms. Clin Immunol. 2011;141:36–48.PubMedCrossRef
168.
Kim TS, Kang YJ, Kim JY, Lee S, Lee WJ, Sohn Y, et al. Up-regulated S100 calcium binding protein A8 in Plasmodium-infected patients correlates with CD4(+)CD25(+)Foxp3 regulatory T cell generation. Malar J. 2015;14:385.PubMedPubMedCentralCrossRef
169.
Savinov AY, Rozanov DV, Strongin AY. Specific inhibition of autoimmune T cell transmigration contributes to beta cell functionality and insulin synthesis in non-obese diabetic (NOD) mice. J Biol Chem. 2007;282:32106–11.PubMedCrossRef
170.
Lozanoska-Ochser B, Peakman M. Level of major histocompatibility complex class I expression on endothelium in non-obese diabetic mice influences CD8 T cell adhesion and migration. Clin Exp Immunol. 2009;157:119–27.PubMedPubMedCentralCrossRef
171.
Matsui T, Oda E, Higashimoto Y, Yamagishi S. Glyceraldehyde-derived pyridinium (GLAP) evokes oxidative stress and inflammatory and thrombogenic reactions in endothelial cells via the interaction with RAGE. Cardiovasc Diabetol. 2015;14:1.PubMedPubMedCentralCrossRef
172.
Sun W, Jiao Y, Cui B, Gao X, Xia Y, Zhao Y. Immune complexes activate human endothelium involving the cell-signaling HMGB1-RAGE axis in the pathogenesis of lupus vasculitis. Lab Investig; J Tech Methods Pathol. 2013;93:626–38.CrossRef
173.
Fiuza C, Bustin M, Talwar S, Tropea M, Gerstenberger E, Shelhamer JH, et al. Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood. 2003;101:2652–60.PubMedCrossRef
174.
Ehlermann P, Eggers K, Bierhaus A, Most P, Weichenhan D, Greten J, et al. Increased proinflammatory endothelial response to S100A8/A9 after preactivation through advanced glycation end products. Cardiovasc Diabetol. 2006;5:6.PubMedPubMedCentralCrossRef
175.
Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, et al. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med. 2003;198:1507–15.PubMedPubMedCentralCrossRef
176.
Frommhold D, Kamphues A, Hepper I, Pruenster M, Lukic IK, Socher I, et al. RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo. Blood. 2010;116:841–9.PubMedCrossRef
177.
Kirstein M, Brett J, Radoff S, Ogawa S, Stern D, Vlassara H. Advanced protein glycosylation induces transendothelial human monocyte chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. Proc Natl Acad Sci U S A. 1990;87:9010–4.PubMedPubMedCentralCrossRef
178.
Lee BW, Chae HY, Kwon SJ, Park SY, Ihm J, Ihm SH. RAGE ligands induce apoptotic cell death of pancreatic beta-cells via oxidative stress. Int J Mol Med. 2010;26:813–8.PubMed
179.
Li M, Song L, Gao X, Chang W, Qin X. Toll-like receptor 4 on islet [beta] cells senses expression changes in high-mobility group box 1 and contributes to the initiation of type 1 diabetes. Exp Mol Med. 2012;44:260–7.PubMedPubMedCentralCrossRef
180.
Luciano Viviani G, Puddu A, Sacchi G, Garuti A, Storace D, Durante A, et al. Glycated fetal calf serum affects the viability of an insulin-secreting cell line in vitro. Metabolism. 2008;57:163–9.PubMedCrossRef
181.
Shu T, Zhu Y, Wang H, Lin Y, Ma Z, Han X. AGEs decrease insulin synthesis in pancreatic beta-cell by repressing Pdx-1 protein expression at the post-translational level. PLoS ONE. 2011;6, e18782.PubMedPubMedCentralCrossRef
182.
Zhao Z, Zhao C, Zhang XH, Zheng F, Cai W, Vlassara H, et al. Advanced glycation end products inhibit glucose-stimulated insulin secretion through nitric oxide-dependent inhibition of cytochrome C oxidase and adenosine triphosphate synthesis. Endocrinology. 2009;150:2569–76.PubMedPubMedCentralCrossRef
Metadata
Title
Receptor for Advanced Glycation End Products (RAGE) in Type 1 Diabetes Pathogenesis
Authors
Sherman S. Leung
Josephine M. Forbes
Danielle J. Borg
Publication date
01-10-2016
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 10/2016
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-016-0782-y

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