Abstract
Diabetes mellitus is a group of metabolic disorders characterized by the presence of hyperglycaemia. Due to its high prevalence and substantial heterogeneity, many studies have been investigating markers that could identify predisposition for the disease development, differentiate between the various subtypes, establish early diagnosis, predict complications or represent novel therapeutic targets. N-glycans, complex oligosaccharide molecules covalently linked to proteins, emerged as potential markers and functional effectors of various diabetes subtypes, appearing to have the capacity to meet these requirements. For instance, it has been shown that N-glycome changes in patients with type 2 diabetes and that N-glycans can even identify individuals with an increased risk for its development. Moreover, genome-wide association studies identified glycosyltransferase genes as candidate causal genes for both type 1 and type 2 diabetes. N-glycans have also been suggested to have a major role in preventing the impairment of glucose-stimulated insulin secretion by modulating cell surface expression of glucose transporters. In this chapter we aimed to describe four major diabetes subtypes: type 1, type 2, gestational and monogenic diabetes, giving an overview of suggested role for N-glycosylation in their development, diagnosis and management.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adua E, Anto EO, Roberts P et al (2018) The potential of N-glycosylation profiles as biomarkers for monitoring the progression of type II diabetes mellitus towards diabetic kidney disease. J Diabetes Metab Disord 17:233–246. https://doi.org/10.1007/s40200-018-0365-3
Aebi M (2013) N-linked protein glycosylation in the ER. Biochim Biophys Acta 1833:2430–2437. https://doi.org/10.1016/j.bbamcr.2013.04.001
Alberti G, Zimmet P, Shaw J et al (2004) Type 2 diabetes in the young: the evolving epidemic: the international diabetes federation consensus workshop. Diabetes Care 27:1798–1811. https://doi.org/10.2337/diacare.27.7.1798
Althari S, Gloyn AL (2015) When is it MODY? Challenges in the interpretation of sequence variants in MODY genes. Rev Diabet Stud 12:330–348. https://doi.org/10.1900/RDS.2015.12.330
Anık A, Çatlı G, Abacı A, Böber E (2015) Maturity-onset diabetes of the young (MODY): an update. J Pediatr Endocrinol Metab 28:251–263. https://doi.org/10.1515/jpem-2014-0384
Axford J (2001) The impact of glycobiology on medicine. Trends Immunol 22:237–239. https://doi.org/10.1016/s1471-4906(01)01890-7
Bermingham ML, Colombo M, McGurnaghan SJ et al (2018) N-glycan profile and kidney disease in type 1 diabetes. Diabetes Care 41:79–87. https://doi.org/10.2337/dc17-1042
Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820. https://doi.org/10.1038/414813a
Bruneau N, Nganga A, Fisher EA, Lombardo D (1997) O-Glycosylation of C-terminal tandem-repeated sequences regulates the secretion of rat pancreatic bile salt-dependent lipase. J Biol Chem 272:27353–27361. https://doi.org/10.1074/jbc.272.43.27353
Câmara NOS, Iseki K, Kramer H et al (2017) Kidney disease and obesity: epidemiology, mechanisms and treatment. Nat Rev Nephrol 13:181–190. https://doi.org/10.1038/nrneph.2016.191
Cameron MJ, Arreaza GA, Zucker P et al (1997) IL-4 prevents insulitis and insulin-dependent diabetes mellitus in nonobese diabetic mice by potentiation of regulatory T helper-2 cell function. J Immunol 159:4686–4692
Catalano PM, Huston L, Amini SB, Kalhan SC (1999) Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am J Obstet Gynecol 180:903–916. https://doi.org/10.1016/s0002-9378(99)70662-9
Chieko M, Gormley AK, Yuhanna IS et al (2005) FcγRIIB mediates C-reactive protein inhibition of endothelial NO synthase. Circ Res 97:1124–1131. https://doi.org/10.1161/01.RES.0000194323.77203.fe
Chien M-W, Lin M-H, Huang S-H et al (2015) Glucosamine modulates T-cell differentiation through down-regulating N-linked glycosylation of CD25. J Biol Chem 290:29329–29344. https://doi.org/10.1074/jbc.M115.674671
Cho NH, Shaw JE, Karuranga S et al (2018) IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138:271–281. https://doi.org/10.1016/j.diabres.2018.02.023
Daly B, Toulis KA, Thomas N et al (2018) Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: a population-based cohort study. PLoS Med 15:e1002488. https://doi.org/10.1371/journal.pmed.1002488
de Queiroz RM, Oliveira IA, Piva B et al (2019) Hexosamine biosynthetic pathway and glycosylation regulate cell migration in melanoma cells. Front Oncol 9. https://doi.org/10.3389/fonc.2019.00116
Debray-Sachs M, Carnaud C, Boitard C et al (1991) Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. J Autoimmun 4:237–248. https://doi.org/10.1016/0896-8411(91)90021-4
DeFronzo RA, Ferrannini E, Groop L et al (2015) Type 2 diabetes mellitus. Nat Rev Dis Primers 1:1–22. https://doi.org/10.1038/nrdp.2015.19
Demetriou M, Granovsky M, Quaggin S, Dennis JW (2001) Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409:733–739. https://doi.org/10.1038/35055582
Dennis JW (1986) Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. Cancer Res 46:5131–5136
Dennis JW, Nabi IR, Demetriou M (2009) Metabolism, cell surface organization, and disease. Cell 139:1229–1241. https://doi.org/10.1016/j.cell.2009.12.008
Dhaliwal R, Weinstock RS (2014) Management of type 1 diabetes in older adults. Diabetes Spectr 27:9–20. https://doi.org/10.2337/diaspect.27.1.9
DiMeglio LA, Evans-Molina C, Oram RA (2018) Type 1 diabetes. Lancet 391:2449–2462. https://doi.org/10.1016/S0140-6736(18)31320-5
Dotz V, Lemmers RFH, Reiding KR et al (2018) Plasma protein N-glycan signatures of type 2 diabetes. Biochim Biophys Acta Gen Subj 1862:2613–2622. https://doi.org/10.1016/j.bbagen.2018.08.005
Ellard S, Lango Allen H, De Franco E et al (2013) Improved genetic testing for monogenic diabetes using targeted next-generation sequencing. Diabetologia 56:1958–1963. https://doi.org/10.1007/s00125-013-2962-5
Elliott MM, Kardana A, Lustbader JW, Cole LA (2007) Carbohydrate and peptide structure of the α- and β-subunits of human chorionic gonadotropin from normal and aberrant pregnancy and choriocarcinoma. Endocrine. https://doi.org/10.1007/BF02778058
Erlich H, Valdes AM, Noble J et al (2008) HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes 57:1084–1092. https://doi.org/10.2337/db07-1331
Ferrer-Admetlla A, Sikora M, Laayouni H et al (2009) A natural history of FUT2 polymorphism in humans. Mol Biol Evol 26:1993–2003. https://doi.org/10.1093/molbev/msp108
Flannick J, Beer NL, Bick AG et al (2013) Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes. Nat Genet 45:1380–1385. https://doi.org/10.1038/ng.2794
Flannick J, Johansson S, Njølstad PR (2016) Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes. Nat Rev Endocrinol 12:394–406. https://doi.org/10.1038/nrendo.2016.50
Forouhi NG, Wareham NJ (2014) Epidemiology of diabetes. Medicine (Abingdon) 42:698–702. https://doi.org/10.1016/j.mpmed.2014.09.007
Fowler MJ (2011) Microvascular and macrovascular complications of diabetes. Clin Diab 29:116–122. https://doi.org/10.2337/diaclin.29.3.116
Georgieff MK, Petry CD, Mills MM et al (1997) Increased N-glycosylation and reduced transferrin-binding capacity of transferrin receptor isolated from placentae of diabetic women. Placenta 18:563–568. https://doi.org/10.1016/0143-4004(77)90011-x
Gornik O, Pavić T, Lauc G (2012) Alternative glycosylation modulates function of IgG and other proteins – implications on evolution and disease. Biochim Biophys Acta 1820:1318–1326. https://doi.org/10.1016/j.bbagen.2011.12.004
Grigorian A, Lee S-U, Tian W et al (2007) Control of T-cell-mediated autoimmunity by metabolite flux to N-glycan biosynthesis. J Biol Chem 282:20027–20035. https://doi.org/10.1074/jbc.M701890200
Haga Y, Ishii K, Suzuki T (2011) N-glycosylation is critical for the stability and intracellular trafficking of glucose transporter GLUT4. J Biol Chem 286:31320–31327. https://doi.org/10.1074/jbc.M111.253955
Harries LW, Ellard S, Stride A et al (2006) Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes. Hum Mol Genet 15:2216–2224. https://doi.org/10.1093/hmg/ddl147
Hassan GA, Sliem HA, Ellethy AT, Salama ME-S (2012) Role of immune system modulation in prevention of type 1 diabetes mellitus. Indian J Endocrinol Metab 16:904–909. https://doi.org/10.4103/2230-8210.102989
Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259:87–91. https://doi.org/10.1126/science.7678183
Ing BL, Chen H, Robinson KA et al (1996) Characterization of a mutant GLUT4 lacking the N-glycosylation site: studies in transfected rat adipose cells. Biochem Biophys Res Commun 218:76–82. https://doi.org/10.1006/bbrc.1996.0015
International Expert Committee (2009) International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32:1327–1334. https://doi.org/10.2337/dc09-9033
Johannes L, Jacob R, Leffler H (2018) Galectins at a glance. J Cell Sci 131. https://doi.org/10.1242/jcs.208884
Juszczak A, Pavić T, Vučković F et al (2019) Plasma fucosylated glycans and C-reactive protein as biomarkers of HNF1A-MODY in young adult–onset nonautoimmune diabetes. Diabetes Care 42:17–26. https://doi.org/10.2337/dc18-0422
Kaburagi T, Kizuka Y, Kitazume S, Taniguchi N (2017) The inhibitory role of α2,6-sialylation in adipogenesis. J Biol Chem 292:2278–2286. https://doi.org/10.1074/jbc.M116.747667
Keser T, Gornik I, Vučković F et al (2017) Increased plasma N-glycome complexity is associated with higher risk of type 2 diabetes. Diabetologia 60:2352–2360. https://doi.org/10.1007/s00125-017-4426-9
Kleinberger JW, Pollin TI (2015) Undiagnosed MODY: time for action. Curr Diab Rep 15:110. https://doi.org/10.1007/s11892-015-0681-7
Kubota T, Kubota N, Kumagai H et al (2011) Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab 13:294–307. https://doi.org/10.1016/j.cmet.2011.01.018
Lau KS, Partridge EA, Grigorian A et al (2007) Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell 129:123–134. https://doi.org/10.1016/j.cell.2007.01.049
Lauc G, Essafi A, Huffman JE et al (2010) Genomics meets glycomics—the first GWAS study of human N-glycome identifies HNF1α as a master regulator of plasma protein fucosylation. PLoS Genet 6:e1001256. https://doi.org/10.1371/journal.pgen.1001256
Lee C-L, Chiu PCN, Pang P-C et al (2011) Glycosylation failure extends to glycoproteins in gestational diabetes mellitus: evidence from reduced α2-6 sialylation and impaired immunomodulatory activities of pregnancy-related glycodelin-A. Diabetes 60:909–917. https://doi.org/10.2337/db10-1186
Lemmers RFH, Vilaj M, Urda D et al (2017) IgG glycan patterns are associated with type 2 diabetes in independent European populations. Biochim Biophys Acta Gen Subj 1861:2240–2249. https://doi.org/10.1016/j.bbagen.2017.06.020
Li X, Wang H, Russell A et al (2019) Type 2 diabetes mellitus is associated with the immunoglobulin G N-glycome through putative proinflammatory mechanisms in an Australian population. OMICS J Integr Biol 23:631–639. https://doi.org/10.1089/omi.2019.0075
Liese AD, Lawson A, Song H-R et al (2010) Evaluating geographic variation in type 1 and type 2 diabetes mellitus incidence in youth in four U.S. regions. Health Place 16:547–556. https://doi.org/10.1016/j.healthplace.2009.12.015
Liu J, Dolikun M, Štambuk J et al (2019) Glycomics for type 2 diabetes biomarker discovery: promise of immunoglobulin G subclass-specific fragment crystallizable N-glycosylation in the Uyghur population. OMICS J Integr Biol 23:640–648. https://doi.org/10.1089/omi.2019.0052
Locke AE, Kahali B, Berndt SI et al (2015) Genetic studies of body mass index yield new insights for obesity biology. Nature 518:197–206. https://doi.org/10.1038/nature14177
Lundgren M, Sahlin Å, Svensson C et al (2014) Reduced morbidity at diagnosis and improved glycemic control in children previously enrolled in DiPiS follow-up. Pediatr Diabetes 15:494–501. https://doi.org/10.1111/pedi.12151
Mahajan A, Taliun D, Thurner M et al (2018) Fine-mapping of an expanded set of type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet 50:1505–1513. https://doi.org/10.1038/s41588-018-0241-6
Marshall S, Bacote V, Traxinger RR (1991) Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 266:4706–4712
Matveyenko AV, Butler PC (2006) β-Cell deficit due to increased apoptosis in the human islet amyloid polypeptide transgenic (HIP) rat recapitulates the metabolic defects present in type 2 diabetes. Diabetes 55:2106–2114. https://doi.org/10.2337/db05-1672
McClain DA (2002) Hexosamines as mediators of nutrient sensing and regulation in diabetes. J Diabetes Complicat 16:72–80. https://doi.org/10.1016/s1056-8727(01)00188-x
McIntosh CHS, Widenmaier S, Kim S-J (2009) Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide; GIP). Vitam Horm 80:409–471. https://doi.org/10.1016/S0083-6729(08)00615-8
McIntyre HD, Catalano P, Zhang C et al (2019) Gestational diabetes mellitus. Nat Rev Dis Primers 5:1–19. https://doi.org/10.1038/s41572-019-0098-8
Michel F, Attal-Bonnefoy G, Mangino G et al (2001) CD28 as a molecular amplifier extending TCR ligation and signaling capabilities. Immunity 15:935–945. https://doi.org/10.1016/S1074-7613(01)00244-8
Morahan G (2012) Insights into type 1 diabetes provided by genetic analyses. Curr Opin Endocrinol Diabetes Obes 19:263–270. https://doi.org/10.1097/MED.0b013e328355b7fe
Mueckler M, Thorens B (2013) The SLC2 (GLUT) family of membrane transporters. Mol Asp Med 34:121–138. https://doi.org/10.1016/j.mam.2012.07.001
Munkley J, Elliott DJ (2016) Hallmarks of glycosylation in cancer. Oncotarget 7:35478–35489. https://doi.org/10.18632/oncotarget.8155
Muoio DM, Newgard CB (2008) Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9:193–205. https://doi.org/10.1038/nrm2327
National Research Council (2012) Transforming Glycoscience: a roadmap for the future
Nauck M, Stöckmann F, Ebert R, Creutzfeldt W (1986) Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 29:46–52. https://doi.org/10.1007/BF02427280
Nisticò L, Buzzetti R, Pritchard LE et al (1996) The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian diabetes registry. Hum Mol Genet 5:1075–1080. https://doi.org/10.1093/hmg/5.7.1075
Ohtsubo K, Takamatsu S, Minowa MT et al (2005) Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. Cell 123:1307–1321. https://doi.org/10.1016/j.cell.2005.09.041
Ohtsubo K, Chen MZ, Olefsky JM, Marth JD (2011) Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport. Nat Med 17:1067–1075. https://doi.org/10.1038/nm.2414
Ohtsubo K, Takamatsu S, Gao C et al (2013) N-glycosylation modulates the membrane sub-domain distribution and activity of glucose transporter 2 in pancreatic beta cells. Biochem Biophys Res Commun 434:346–351. https://doi.org/10.1016/j.bbrc.2013.03.076
Olson AL (2012) Regulation of GLUT4 and insulin-dependent glucose flux. ISRN Mol Biol 2012. https://doi.org/10.5402/2012/856987
Onengut-Gumuscu S, Chen W-M, Burren O et al (2015) Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat Genet 47:381–386. https://doi.org/10.1038/ng.3245
Paprott R, Mühlenbruch K, Mensink GBM et al (2016) Validation of the German diabetes risk score among the general adult population: findings from the German health interview and examination surveys. BMJ Open Diabetes Res Care 4. https://doi.org/10.1136/bmjdrc-2016-000280
Parker BL, Thaysen-Andersen M, Fazakerley DJ et al (2016) Terminal galactosylation and sialylation switching on membrane glycoproteins upon TNF-alpha-induced insulin resistance in adipocytes. Mol Cell Proteomics 15:141–153. https://doi.org/10.1074/mcp.M115.054221
Patterson CC, Dahlquist GG, Gyürüs E et al (2009) Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet 373:2027–2033. https://doi.org/10.1016/S0140-6736(09)60568-7
Pavić T, Juszczak A, Pape Medvidović E et al (2018) Maturity onset diabetes of the young due to HNF1A variants in Croatia. Biochemia Medica In press
Poland D, Schalkwijk C, Stehouwer C et al (2001) Increased alpha3-fucosylation of alpha1-acid glycoprotein in type I diabetic patients is related to vascular function. Glycoconj J 18:261–268. https://doi.org/10.1023/A:1012412908983
Pozzilli P, Guglielmi C (2009) Double diabetes: a mixture of type 1 and type 2 diabetes in youth. Endocr Dev 14:151–166. https://doi.org/10.1159/000207484
Pozzilli P, Pieralice S (2018) Latent autoimmune diabetes in adults: current status and new horizons. Endocrinol Metab (Seoul) 33:147–159. https://doi.org/10.3803/EnM.2018.33.2.147
Pulgaron ER, Delamater AM (2014) Obesity and type 2 diabetes in children: epidemiology and treatment. Curr Diab Rep 14:508. https://doi.org/10.1007/s11892-014-0508-y
Reily C, Stewart TJ, Renfrow MB, Novak J (2019) Glycosylation in health and disease. Nat Rev Nephrol 15:346–366. https://doi.org/10.1038/s41581-019-0129-4
Rodriguez BL, Abbott RD, Fujimoto W et al (2002) The American Diabetes Association and World Health Organization classifications for diabetes: their impact on diabetes prevalence and total and cardiovascular disease mortality in elderly Japanese-American men. Diabetes Care 25:951–955. https://doi.org/10.2337/diacare.25.6.951
Rosen ED, Spiegelman BM (2014) What we talk about when we talk about fat. Cell 156:20–44. https://doi.org/10.1016/j.cell.2013.12.012
Royle L, Campbell MP, Radcliffe CM et al (2008) HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database software. Anal Biochem 376:1–12. https://doi.org/10.1016/j.ab.2007.12.012
Rudman N, Gornik O, Lauc G (2019) Altered N-glycosylation profiles as potential biomarkers and drug targets in diabetes. FEBS Lett 593:1598–1615. https://doi.org/10.1002/1873-3468.13495
Shields BM, Hicks S, Shepherd MH et al (2010) Maturity-onset diabetes of the young (MODY): how many cases are we missing? Diabetologia 53:2504–2508. https://doi.org/10.1007/s00125-010-1799-4
Shungin D, Winkler TW, Croteau-Chonka DC et al (2015) New genetic loci link adipose and insulin biology to body fat distribution. Nature 518:187–196. https://doi.org/10.1038/nature14132
Singh SS, Heijmans R, Meulen CKE et al (2020) Association of the IgG N-glycome with the course of kidney function in type 2 diabetes. BMJ Open Diabetes Res Care 8:e001026. https://doi.org/10.1136/bmjdrc-2019-001026
Smilowitz JT, Totten SM, Huang J et al (2013) Human milk secretory immunoglobulin a and lactoferrin N-glycans are altered in women with gestational diabetes mellitus. J Nutr 143:1906–1912. https://doi.org/10.3945/jn.113.180695
Smyth DJ, Cooper JD, Howson JMM et al (2011) FUT2 nonsecretor status links type 1 diabetes susceptibility and resistance to infection. Diabetes 60:3081–3084. https://doi.org/10.2337/db11-0638
Stein SA, Maloney KL, Pollin TI (2014) Genetic counseling for diabetes mellitus. Curr Genet Med Rep 2:56–67. https://doi.org/10.1007/s40142-014-0039-5
Tanigaki K, Sacharidou A, Peng J et al (2018) Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance. J Clin Invest 128:309–322. https://doi.org/10.1172/JCI89333
Testa R, Bonfigli AR, Prattichizzo F et al (2017) The “metabolic memory” theory and the early treatment of hyperglycemia in prevention of diabetic complications. Nutrients 9. https://doi.org/10.3390/nu9050437
Thanabalasingham G, Huffman JE, Kattla JJ et al (2013) Mutations in HNF1A result in marked alterations of plasma glycan profile. Diabetes 62:1329–1337. https://doi.org/10.2337/db12-0880
The American Diabetes Association (2020) Classification and diagnosis of diabetes: standards of medical Care in diabetes—2020. Diabetes Care 43:S14–S31. https://doi.org/10.2337/dc20-S002
Traxinger RR, Marshall S (1991) Coordinated regulation of glutamine:fructose-6-phosphate amidotransferase activity by insulin, glucose, and glutamine. Role of hexosamine biosynthesis in enzyme regulation. J Biol Chem 266:10148–10154
Ulrich P, Cerami A (2001) Protein glycation, diabetes, and aging. Recent Prog Horm Res 56:1–21. https://doi.org/10.1210/rp.56.1.1
Varki A, Cummings RD, Esko JD et al (2015) Essentials of glycobiology, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor
Vassy JL, DasMahapatra P, Meigs JB et al (2012) Genotype prediction of adult type 2 diabetes from adolescence in a multiracial population. Pediatrics 130:e1235–e1242. https://doi.org/10.1542/peds.2012-1132
Wahl A, van den Akker E, Klaric L et al (2018) Genome-wide association study on immunoglobulin G glycosylation patterns. Front Immunol 9:277. https://doi.org/10.3389/fimmu.2018.00277
Whitaker GM, Lynn FC, McIntosh CHS, Accili EA (2012) Regulation of GIP and GLP1 receptor cell surface expression by N-glycosylation and receptor heteromerization. PLoS One 7:e32675. https://doi.org/10.1371/journal.pone.0032675
Winer DA, Winer S, Shen L et al (2011) B-cells promote insulin resistance through modulation of T-cells and production of pathogenic IgG antibodies. Nat Med 17:610–617. https://doi.org/10.1038/nm.2353
Wittenbecher C, Štambuk T, Kuxhaus O et al (2020) Plasma N-glycans as emerging biomarkers of cardiometabolic risk: a prospective investigation in the EPIC-Potsdam Cohort Study. Diabetes Care 43:661–668. https://doi.org/10.2337/dc19-1507
Wolters-Eisfeld G, Mercanoglu B, Hofmann BT et al (2018) Loss of complex O-glycosylation impairs exocrine pancreatic function and induces MODY8-like diabetes in mice. Exp Mol Med 50:1–13. https://doi.org/10.1038/s12276-018-0157-3
Yi Z, Li L, Garland A et al (2012) IFN-γ receptor deficiency prevents diabetes induction by diabetogenic CD4+ T-cells but not CD8+ T-cells1. Eur J Immunol 42:2010–2018. https://doi.org/10.1002/eji.201242374
Yki-Järvinen H, Virkamäki A, Daniels MC et al (1998) Insulin and glucosamine infusions increase O-linked N-acetyl-glucosamine in skeletal muscle proteins in vivo. Metabolism 47:449–455. https://doi.org/10.1016/s0026-0495(98)90058-0
Zaarour N, Berenguer M, Le Marchand-Brustel Y, Govers R (2012) Deciphering the role of GLUT4 N-glycosylation in adipocyte and muscle cell models. Biochem J 445:265–273. https://doi.org/10.1042/BJ20120232
Zhu Y, Zhang C (2016) Prevalence of gestational diabetes and risk of progression to type 2 diabetes: a global perspective. Curr Diab Rep 16:7. https://doi.org/10.1007/s11892-015-0699-x
Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479. https://doi.org/10.1001/jama.2013.6285
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Štambuk, T., Gornik, O. (2021). Protein Glycosylation in Diabetes. In: Lauc, G., Trbojević-Akmačić, I. (eds) The Role of Glycosylation in Health and Disease. Advances in Experimental Medicine and Biology, vol 1325. Springer, Cham. https://doi.org/10.1007/978-3-030-70115-4_14
Download citation
DOI: https://doi.org/10.1007/978-3-030-70115-4_14
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-70114-7
Online ISBN: 978-3-030-70115-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)