1. Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med 2015; 278: 369–395. doi: 10.1111/joim.12395.
2.
Fonolleda M, Murillo M, Vázquez F, et al. Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers. Horm Res Paediatr 2017; 88: 307–315. doi: 10.1159/000479030.
3.
Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med 2013; 30: 803–817. doi: 10.1111/dme.12159.
4.
Zhong T, Tang R, Gong S, et al. The remission phase in type 1 diabetes: Changing epidemiology, definitions, and emerging immuno-metabolic mechanisms. Diabetes Metab Res Rev 2020; 36: e3207. doi: 10.1002/dmrr.3207.
5.
Moosavi M, Séguin J, Polychronakos C. Effect of autoimmunity risk loci on the honeymoon phase in type 1 diabetes. Pediatr Diabetes 2017; 18: 459–462. doi: 10.1111/pedi.12421.
6.
Stanescu DE, Lord K, Lipman TH. The epidemiology of type 1 diabetes in children. Endocrinol Metab Clin North Am 2012; 41: 679–694. doi: 10.1016/j.ecl.2012.08.001.
7.
Karjalainen J, Salmela P, Ilonen J, et al. A comparison of childhood and adult type I diabetes mellitus. N Engl J Med. 1989; 320: 881–886. doi: 10.1056/NEJM198904063201401.
8.
Ferguson SC, Blane A, Wardlaw J, et al. Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function. Diabetes Care 2005; 28: 1431–1437. doi: 10.2337/diacare.28.6.1431.
9.
Syed FZ. Type 1 Diabetes Mellitus. Ann Intern Med 2022; 175: ITC33-ITC48. doi: 10.7326/AITC202203150.
10.
Quattrin T, Mastrandrea LD, Walker LSK. Type 1 diabetes. Lancet 2023; 401: 2149–2162. doi: 10.1016/S0140-6736(23)00223-4.
11.
Svärd AA. Immunological markers of type 1 diabetes pathogenesis prior to clinical diagnosis. Doctoral dissertation. Lund Univeristy 2022.
12.
Wherrett DK, Daneman D. Prevention of type 1 diabetes. Endocrinol Metab Clin North Am 2009; 38: 777–790. doi: 10.1016/j.ecl.2009.08.006.
13.
Tuomilehto J, Ogle GD, Lund-Blix NA, Stene LC. Update on Worldwide Trends in Occurrence of Childhood Type 1 Diabetes in 2020. Pediatr Endocrinol Rev 2020; 17 (Suppl 1): 198–209. doi: 10.17458/per.vol17.2020.tol.epidemiologychildtype1diabetes.
14.
Kondrashova A, Hyöty H. Role of viruses and other microbes in the pathogenesis of type 1 diabetes. Int Rev Immunol 2014; 33: 284–295. doi: 10.3109/08830185.2014.889130.
15.
Heninger AK, Eugster A, Kuehn D, et al. A divergent population of autoantigen-responsive CD4+ T cells in infants prior to β cell autoimmunity. Sci Transl Med 2017; 9: eaaf8848. doi: 10.1126/scitranslmed.aaf8848.
16.
Mortensen HB, Swift PG, Holl RW, et al. Multinational study in children and adolescents with newly diagnosed type 1 diabetes: association of age, ketoacidosis, HLA status, and autoantibodies on residual beta-cell function and glycemic control 12 months after diagnosis. Pediatr Diabetes 2010; 11: 218–226. doi: 10.1111/j.1399-5448.2009.00566.x
17.
Chen YC, Tung YC, Liu SY, et al. Clinical characteristics of type 1 diabetes mellitus in Taiwanese children aged younger than 6 years: A single-center experience. J Formos Med Assoc 2017; 116: 340–344. doi: 10.1016/j.jfma.2016.07.005.
18.
Niedzwiecki P, Pilacinski S, Uruska A, et al. Influence of remission and its duration on development of early microvascular complications in young adults with type 1 diabetes. J Diabetes Complications 2015; 29: 1105–1111. doi: 10.1016/j.jdiacomp.2015.09.002.
19.
Cengiz E, Cheng P, Ruedy KJ, et al. Clinical outcomes in youth beyond the first year of type 1 diabetes: Results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study. Pediatr Diabetes 2017; 18: 566–573. doi: 10.1111/pedi.12459.
20.
Nagl K, Hermann JM, Plamper M, et al. Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose-adjusted HbA1c in 3657 children and adolescents from Germany and Austria. Pediatr Diabetes 2017; 18: 428–434. doi: 10.1111/pedi.12413.
21.
Ortqvist E, Falorni A, Scheynius A, et al. Age governs gender-dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM. Acta Paediatr 1997; 86: 1166–1171. doi: 10.1111/j.1651-2227.1997.tb14837.x.
22.
Abdul-Rasoul M, Habib H, Al-Khouly M. “The honeymoon phase” in children with type 1 diabetes mellitus: frequency, duration, and influential factors. Pediatr Diabetes 2006; 7: 101–107. doi: 10.1111/j.1399-543X.2006.00155.x.
23.
Neylon OM, White M, O Connell MA, Cameron FJ. Insulin-dose-adjusted HbA1c-defined partial remission phase in a paediatric population – when is the honeymoon over? Diabet Med 2013; 30: 627–628. doi: 10.1111/dme.12097.
24.
Moole H, Moole V, Mamidipalli A, et al. Spontaneous complete remission of type 1 diabetes mellitus in an adult – review and case report. J Community Hosp Intern Med Perspect 2015; 5: 28709. doi: 10.3402/jchimp.v5.28709.
25.
Pozzilli P, Manfrini S, Buzzetti R, et al. Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study. Diabetes Res Clin Pract 2005; 68: 258–264. doi: 10.1016/j.diabres.2004.10.001.
26.
Mortensen HB, Hougaard P, Swift P, et al. New definition for the partial remission period in children and adolescents with type 1 diabetes. Diabetes Care 2009; 32: 1384–1390. doi: 10.2337/dc08-1987.
27.
Max Andersen ML, Hougaard P, Pörksen S, et al. Partial remission definition: validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish children with new-onset type 1 diabetes. Pediatr Diabetes 2014; 15: 469–476. doi: 10.1111/pedi.12208.
28.
Muhammad BJ, Swift PG, Raymond NT, Botha JL. Partial remission phase of diabetes in children younger than age 10 years. Arch Dis Child 1999; 80: 367–369. doi: 10.1136/adc.80.4.367.
29.
Knip M, Puukka R, Käär ML, Akerblom HK. Remission phase, endogenous insulin secretion and metabolic control in diabetic children. Acta Diabetol Lat 1982; 19: 243–251. doi: 10.1007/BF02624684.
30.
Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 1998; 12: 517–523. doi: 10.7326/0003-4819-128-7-199804010-00001.
31.
Thrailkill KM, Moreau CS, Swearingen C, et al. Insulin pump therapy started at the time of diagnosis: effects on glycemic control and pancreatic β-cell function in type 1 diabetes. Diabetes Technol Ther 2011; 13: 1023–1030. doi: 10.1089/dia.2011.0085.
32.
Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care 1990; 13: 610–630. doi: 10.2337/diacare.13.6.610.
33.
Gray RS, Cowan P, Duncan LJ, Clarke BF. Reversal of insulin resistance in type 1 diabetes following initiation of insulin treatment. Diabet Med 1986; 3: 18–23. doi: 10.1111/j.1464-5491.1986.tb00699.x.
34.
Schloot NC, Hanifi-Moghaddam P, Aabenhus-Andersen N, et al. Association of immune mediators at diagnosis of Type 1 diabetes with later clinical remission. Diabet Med 2007; 24: 512–520. doi: 10.1111/j.1464-5491.2007.02096.x.
35.
Pfleger C, Mortensen HB, Hansen L, et al. Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes. Diabetes 2008; 57: 929–937. doi: 10.2337/db07-1697.
36.
Arrieta-Blanco FJ, Pulido N, Suarez A, et al. High glucose uptake by adipocytes in a type 1 diabetic patient with a partial ‘honeymoon’ period. Diabet Med. 1998; 15: 788–790. doi: 10.1002/(SICI)1096-9136(199809)15:9<788::AID-DIA666>3.0.CO; 2-I.
37.
Akirav E, Kushner JA, Herold KC. Beta-cell mass and type 1 diabetes: going, going, gone? Diabetes 2008; 57: 2883–2888. doi: 10.2337/db07-1817.
38.
Pfleger C, Mortensen HB, Hansen L, et al. Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes. Diabetes 2008; 57: 929–937. doi: 10.2337/db07-1697.
39.
Karges B, Durinovic-Belló I, Heinze E, et al. Immunological mechanisms associated with long-term remission of human type 1 diabetes. Diabetes Metab Res Rev 2006; 22: 184–189. doi: 10.1002/dmrr.600.
40.
Alizadeh BZ, Hanifi-Moghaddam P, Eerligh P, et al. Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes. Clin Exp Immunol 2006; 145: 480–484. doi: 10.1111/j.1365-2249.2006.03172.x.
41.
Pfleger C, Kaas A, Hansen L, et al. Relation of circulating concentrations of chemokine receptor CCR5 ligands to C-peptide, proinsulin and HbA1c and disease progression in type 1 diabetes. Clin Immunol 2008; 128: 57–65. doi: 10.1016/j.clim.2008.03.458.
42.
Atkinson MA, Roep BO, Posgai A, et al. The challenge of modulating β-cell autoimmunity in type 1 diabetes. Lancet Diabetes Endocrinol 2019; 7: 52–64. doi: 10.1016/S2213-8587(18)30112-8.
43.
Fife BT, Guleria I, Gubbels Bupp M, et al. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway. J Exp Med 2006; 203: 2737–2747. doi: 10.1084/jem.20061577.
44.
Li X, Zhong T, Tang R, et al. PD-1 and PD-L1 Expression in Peripheral CD4/CD8+ T Cells Is Restored in the Partial Remission Phase in Type 1 Diabetes. J Clin Endocrinol Metab 2020; 105: dgaa130. doi: 10.1210/clinem/dgaa130.
45.
Ben Nasr M, Tezza S, D’Addio F, et al. PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes. Sci Transl Med. 2017; 9: eaam7543. doi: 10.1126/scitranslmed.aam7543.
46.
Moya R, Robertson HK, Payne D, et al. A pilot study showing associations between frequency of CD4(+) memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes. Clin Immunol 2016; 166–167: 72–80. doi: 10.1016/j.clim.2016.04.012.
47.
Fletcher JM, Lonergan R, Costelloe L, et al. CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol 2009; 183: 7602–7610. doi: 10.4049/jimmunol.0901881.
48.
Glisic-Milosavljevic S, Wang T, Koppen M, et al. Dynamic changes in CD4+ CD25+(high) T cell apoptosis after the diagnosis of type 1 diabetes. Clin Exp Immunol. 2007; 150: 75–82. doi: 10.1111/j.1365-2249.2007.03475.x.
49.
Glisic-Milosavljevic S, Waukau J, Jailwala P, et al. At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction. PLoS One 2007; 2: e146. doi: 10.1371/journal.pone.0000146.
50.
Campbell-Thompson M, Fu A, Kaddis JS, et al. Insulitis and b-Cell Mass in the Natural History of Type 1 Diabetes. Diabetes 2016; 65: 719–731. doi: 10.2337/db15-0779.
51.
Rui J, Deng S, Arazi A, et al. b Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice. Cell Metab 2017; 25: 727–738. doi: 10.1016/j.cmet.2017.01.005.
52.
Fitas AL, Martins C, Borrego LM, et al. Immune cell and cytokine patterns in children with type 1 diabetes mellitus undergoing a remission phase: A longitudinal study. Pediatr Diabetes 2018; 19: 963–971. doi: 10.1111/pedi.12671.
53.
Villalba A, Fonolleda M, Murillo M, et al. Partial remission and early stages of pediatric type 1 diabetes display immunoregulatory changes. A pilot study. Transl Res 2019; 210: 8–25. doi: 10.1016/j.trsl.2019.03.002.
54.
Brown RJ, Rother KI. Effects of beta-cell rest on beta-cell function: a review of clinical and preclinical data. Pediatr Diabetes 2008; 9: 14–22. doi: 10.1111/j.1399-5448.2007.00272.x.
55.
Lombardo F, Valenzise M, Wasniewska M, et al. Two-year prospective evaluation of the factors affecting honeymoon frequency and duration in children with insulin dependent diabetes mellitus: the key-role of age at diagnosis. Diabetes Nutr Metab 2002; 15: 246–251.
56.
Aly H, Gottlieb P. The honeymoon phase: intersection of metabolism and immunology. Curr Opin Endocrinol Diabetes Obes 2009; 16: 286–292. doi: 10.1097/MED.0b013e32832e0693.
57.
Krogvold L, Skog O, Sundström G, et al. Function of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes: Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Vitro: Results From the DiViD Study. Diabetes. 2015; 64(7):2506-2512. doi: 10.2337/db14-1911.
58.
von Herrath M, Sanda S, Herold K. Type 1 diabetes as a relapsing-remitting disease?. Nat Rev Immunol. 2007; 7(12):988-994. doi: 10.1038/nri2192.
59.
Chobot A, Stompór J, Szyda K, et al. Remission phase in children diagnosed with type 1 diabetes in years 2012 to 2013 in Silesia, Poland: An observational study. Pediatr Diabetes 2019; 20: 286–292. doi: 10.1111/pedi.12824.
60.
Habib T, Long SA, Samuels PL, et al. Dynamic Immune Phenotypes of B and T Helper Cells Mark Distinct Stages of T1D Progression. Diabetes 2019; 68: 1240–1250. doi: 10.2337/db18-1081.
61.
Deng C, Xiang Y, Tan T, et al. Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults. Diabetes Care 2016; 39: 434–440. doi: 10.2337/dc15-1765.
62.
Kurozumi A, Okada Y, Arao T, et al. Pancreas-protective effect of rituximab for acute-onset type 1 diabetes in the honeymoon period: a case report. Endocrinol Diabetes Metab Case Rep 2016; 2016: 160020. doi: 10.1530/EDM-16-0020.
63.
Nataraj C, Thomas DW, Tilley SL, et al. Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest 2001; 108: 1229–1235. doi: 10.1172/JCI13640.
64.
Takayama K, García-Cardena G, Sukhova GK, et al. Prostaglandin E2 suppresses chemokine production in human macrophages through the EP4 receptor. J Biol Chem 2002; 277: 44147–44154. doi: 10.1074/jbc.M204810200.
65.
Sugimoto Y, Narumiya S. Prostaglandin E receptors. J Biol Chem. 2007; 282: 11613–11617. doi: 10.1074/jbc.R600038200.
66.
Amer M, Bead VR, Bathon J, et al. Use of nonsteroidal anti-inflammatory drugs in patients with cardiovascular disease: a cautionary tale. Cardiol Rev 2010; 18: 204–212. doi: 10.1097/CRD.0b013e3181ce1521.
67.
Holmes DR, Wester W, Thompson RW, Reilly JM. Prostaglandin E2 synthesis and cyclooxygenase expression in abdominal aortic aneurysms. J Vasc Surg 1997; 25: 810–815. doi: 10.1016/s0741-5214(97)70210-6.
68.
Samuelsson B, Morgenstern R, Jakobsson PJ. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 2007; 59: 207–224. doi: 10.1124/pr.59.3.1.
69.
Coleman RA, Grix SP, Head SA, et al. A novel inhibitory prostanoid receptor in piglet saphenous vein. Prostaglandins 1994; 47: 151–168. doi: 10.1016/0090-6980(94)90084-1.
70.
Hristovska AM, Rasmussen LE, Hansen PB, et al. Prostaglandin E2 induces vascular relaxation by E-prostanoid 4 receptor-mediated activation of endothelial nitric oxide synthase. Hypertension 2007; 50: 525–530. doi: 10.1161/HYPERTENSIONAHA.107.088948.
71.
Zhang Y, Daaka Y. PGE2 promotes angiogenesis through EP4 and PKA Cγ pathway. Blood 2011; 118: 5355–5364. doi: 10.1182/blood-2011-04-350587.
72.
Johannessen M, Delghandi MP, Moens U. What turns CREB on? Cell Signal 2004; 16: 1211–1227. doi: 10.1016/j.cellsig.2004.05.001.
73.
Johannessen M, Moens U. Multisite phosphorylation of the cAMP response element-binding protein (CREB) by a diversity of protein kinases. Front Biosci 2007; 12: 1814–1832. doi: 10.2741/2190.
74.
Hazan-Eitan Z, Weinstein Y, Hadad N, et al. Induction of Fc gammaRIIA expression in myeloid PLB cells during differentiation depends on cytosolic phospholipase A2 activity and is regulated via activation of CREB by PGE2. Blood 2006; 108: 1758–1766. doi: 10.1182/blood-2006-05-021881.
75.
Côté SC, Pasvanis S, Bounou S, Dumais N. CCR7-specific migration to CCL19 and CCL21 is induced by PGE(2) stimulation in human monocytes: Involvement of EP(2)/EP(4) receptors activation. Mol Immunol 2009; 46: 2682–2693. doi: 10.1016/j.molimm.2008.08.269.
76.
Stock A, Booth S, Cerundolo V. Prostaglandin E2 suppresses the differentiation of retinoic acid-producing dendritic cells in mice and humans. J Exp Med 2011; 208: 761–773. doi: 10.1084/jem.20101967.
77.
Bos JL. Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 2003; 4: 733–738. doi: 10.1038/nrm1197.
78.
Yokoyama U, Minamisawa S, Quan H, et al. Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A. J Biol Chem 2008; 283: 28702–28709. doi: 10.1074/jbc.M804223200.
79.
Faour WH, Gomi K, Kennedy CR. PGE(2) induces COX-2 expression in podocytes via the EP(4) receptor through a PKA-independent mechanism. Cell Signal. 2008; 20: 2156–2164. doi: 10.1016/j.cellsig.2008.08.007.
80.
Desai S, Ashby B. Agonist-induced internalization and mitogen-activated protein kinase activation of the human prostaglandin EP4 receptor. FEBS Lett 2001; 501: 156–160. doi: 10.1016/s0014-5793(01)02640-0.
81.
Takayama K, Sukhova GK, Chin MT, Libby P. A novel prostaglandin E receptor 4-associated protein participates in antiinflammatory signaling. Circ Res 2006; 98: 499–504. doi: 10.1161/01.RES.0000204451.88147.96.
82.
Ludwig A, Ehlert JE, Flad HD, Brandt E. Identification of distinct surface-expressed and intracellular CXC-chemokine receptor 2 glycoforms in neutrophils: N-glycosylation is essential for maintenance of receptor surface expression. J Immunol 2000; 165: 1044–1052. doi: 10.4049/jimmunol.165.2.1044.
83.
Bastepe M, Ashby B. Identification of a region of the C-terminal domain involved in short-term desensitization of the prostaglandin EP4 receptor. Br J Pharmacol 1999; 126: 365–371. doi: 10.1038/sj.bjp.0702291.
84.
Desai S, April H, Nwaneshiudu C, Ashby B. Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration. Mol Pharmacol 2000; 58: 1279–1286. doi: 10.1124/mol.58.6.1279.
85.
Buchanan FG, Gorden DL, Matta P, Shi Q, Matrisian LM, DuBois RN. Role of beta-arrestin 1 in the metastatic progression of colorectal cancer. Proc Natl Acad Sci U S A 2006; 103: 1492–1497. doi: 10.1073/pnas.0510562103.
86.
Fujino H, Xu W, Regan JW. Prostaglandin E2 induced functional expression of early growth response factor-1 by EP4, but not EP2, prostanoid receptors via the phosphatidylinositol 3-kinase and extracellular signal-regulated kinases. J Biol Chem 2003; 278: 12151–12156. doi: 10.1074/jbc.M212665200
87.
Fujino H, Regan JW. EP(4) prostanoid receptor coupling to a pertussis toxin-sensitive inhibitory G protein. Mol Pharmacol 2006; 69: 5–10. doi: 10.1124/mol.105.017749.
88.
Rao R, Redha R, Macias-Perez I, et al. Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem 2007; 282: 16959–16968. doi: 10.1074/jbc.M701214200.
89.
Liang X, Lin L, Woodling NS, et al. Signaling via the prostaglandin E₂ receptor EP4 exerts neuronal and vascular protection in a mouse model of cerebral ischemia. J Clin Invest. 2011; 121: 4362–4371. doi: 10.1172/JCI46279.
90.
Luschnig-Schratl P, Sturm EM, Konya V, et al. EP4 receptor stimulation down-regulates human eosinophil function. Cell Mol Life Sci 2011; 68: 3573–3587. doi: 10.1007/s00018-011-0642-5.
91.
Minami M, Shimizu K, Okamoto Y, et al. Prostaglandin E receptor type 4-associated protein interacts directly with NF-kappaB1 and attenuates macrophage activation. J Biol Chem 2008; 283: 9692–9703. doi: 10.1074/jbc.M709663200.
92.
Prijatelj M, Celhar T, Gobec M, Mlinaric-Rascan I. EP4 receptor signalling in immature B cells involves cAMP and NF-κB dependent pathways. J Pharm Pharmacol 2012; 64: 1090–1098. doi: 10.1111/j.2042-7158.2012.01499.x.
93.
Bradshaw EM, Raddassi K, Elyaman W, et al. Monocytes from patients with type 1 diabetes spontaneously secrete proinflammatory cytokines inducing Th17 cells. J Immunol 2009; 183: 4432–4439. doi: 10.4049/jimmunol.0900576.
94.
Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 2015; 21: 677–687. doi: 10.1038/nm.3893.
95.
Sokolowska M, Chen LY, Liu Y, et al. Prostaglandin E2 Inhibits NLRP3 Inflammasome Activation through EP4 Receptor and Intracellular Cyclic AMP in Human Macrophages. J Immunol 2015; 194: 5472–5487. doi: 10.4049/jimmunol.1401343.
96.
Tang EH, Libby P, Vanhoutte PM, Xu A. Anti-inflammation therapy by activation of prostaglandin EP4 receptor in cardiovascular and other inflammatory diseases. J Cardiovasc Pharmacol 2012; 59: 116–123. doi: 10.1097/FJC.0b013e3182244a12.
97.
Rahman MJ, Rodrigues KB, Quiel JA, et al. Restoration of the type I IFN-IL-1 balance through targeted blockade of PTGER4 inhibits autoimmunity in NOD mice. JCI Insight 2018; 3: e97843. doi: 10.1172/jci.insight.97843.
98.
Ferris ST, Zakharov PN, Wan X, et al. The islet-resident macrophage is in an inflammatory state and senses microbial products in blood. J Exp Med 2017; 214: 2369–2385. doi: 10.1084/jem.20170074.
99.
Moran A, Bundy B, Becker DJ, et al. Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials. Lancet. 2013; 381: 1905–1915. doi: 10.1016/S0140-6736(13)60023-9.
100.
Mayer-Barber KD, Andrade BB, Oland SD, et al. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature 2014; 511: 99–103. doi: 10.1038/nature13489.
101.
Mayer-Barber KD, Yan B. Clash of the Cytokine Titans: counter-regulation of interleukin-1 and type I interferon-mediated inflammatory responses. Cell Mol Immunol 2017; 14: 22–35. doi: 10.1038/cmi.2016.25.
102.
Ku CL, von Bernuth H, Picard C, et al. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J Exp Med 2007; 204: 2407–2422. doi: 10.1084/jem.20070628.
103.
Le Page C, Génin P, Baines MG, Hiscott J. Interferon activation and innate immunity. Rev Immunogenet 2000; 2: 374–386.
104.
Yasui-Kato M, Patlada S, Yokode M, et al. EP4 signalling is essential for controlling islet inflammation by causing a shift in macrophage polarization in obesity/type 2 diabetes. Diab Vasc Dis Res 2020; 17: 1479164120945675. doi: 10.1177/1479164120945675.
105.
Eguchi K, Manabe I, Oishi-Tanaka Y, et al. Saturated fatty acid and TLR signaling link β cell dysfunction and islet inflammation. Cell Metab 2012; 15: 518–533. doi: 10.1016/j.cmet.2012.01.023.
106.
Cucak H, Grunnet LG, Rosendahl A. Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization. J Leukoc Biol 2014; 95: 149–160. doi: 10.1189/jlb.0213075.
107.
Fujisaka S, Usui I, Bukhari A, et al. Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 2009; 58: 2574–2582. doi: 10.2337/db08-1475.
108.
Yasui M, Tamura Y, Minami M, et al. The Prostaglandin E2 Receptor EP4 Regulates Obesity-Related Inflammation and Insulin Sensitivity. PLoS One. 2015; 10: e0136304. doi: 10.1371/journal.pone.0136304.
109.
Heitmeier MR, Kelly CB, Ensor NJ, et al. Role of cyclooxygenase-2 in cytokine-induced beta-cell dysfunction and damage by isolated rat and human islets. J Biol Chem 2004; 279: 53145–53151. doi: 10.1074/jbc.M410978200.
110.
Luo C, Kallajoki M, Gross R, et al. Cellular distribution and contribution of cyclooxygenase COX-2 to diabetogenesis in NOD mouse. Cell Tissue Res 2002; 310: 169–175. doi: 10.1007/s00441-002-0628-6.
111.
Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000; 69: 145–182. doi: 10.1146/annurev.biochem.69.1.145.
112.
Narumiya S. Molecular diversity of prostanoid receptors; subtypes and isoforms of prostaglandin E receptor. Adv Exp Med Biol. 1997; 400A: 207–213. doi: 10.1007/978-1-4615-5325-0_30.
113.
Persaud SJ, Muller D, Belin VD, et al. The role of arachidonic acid and its metabolites in insulin secretion from human islets of Langerhans. Diabetes 2007; 56: 197–203. doi: 10.2337/db06-0490.
114.
Han X, Chen S, Sun Y, Nadler JL, Bleich D. Induction of cyclooxygenase-2 gene in pancreatic beta-cells by 12-lipoxygenase pathway product 12-hydroxyeicosatetraenoic acid. Mol Endocrinol 2002; 16: 2145–2154. doi: 10.1210/me.2001-0300.
115.
Metz SA, Robertson RP, Fujimoto WY. Inhibition of prostaglandin E synthesis augments glucose-induced insulin secretion is cultured pancreas. Diabetes 1981; 30: 551–557. doi: 10.2337/diab.30.7.551.
116.
Meng ZX, Sun JX, Ling JJ, et al. Prostaglandin E2 regulates Foxo activity via the Akt pathway: implications for pancreatic islet beta cell dysfunction. Diabetologia 2006; 49: 2959–2968. doi: 10.1007/s00125-006-0447-5.
117.
Wu CT, Hilgendorf KI, Bevacqua RJ, et al. Discovery of ciliary G protein-coupled receptors regulating pancreatic islet insulin and glucagon secretion. Genes Dev 2021; 35: 1243–1255. doi: 10.1101/gad.348261.121.
118.
Hilgendorf KI, Johnson CT, Jackson PK. The primary cilium as a cellular receiver: organizing ciliary GPCR signaling. Curr Opin Cell Biol 2016; 39: 84–92. doi:10.1016/j.ceb.2016.02.008.
119.
Cano DA, Murcia NS, Pazour GJ, Hebrok M. Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development. 2004; 131: 3457–3467. doi: 10.1242/dev.01189.
120.
Nesmith JE, Hostelley TL, Leitch CC, et al. Genomic knockout of alms1 in zebrafish recapitulates Alström syndrome and provides insight into metabolic phenotypes. Hum Mol Genet 2019; 28: 2212–2223. doi: 10.1093/hmg/ddz053.
121.
Pietrzak-Nowacka M, Safranow K, Byra E, et al. Glucose metabolism parameters during an oral glucose tolerance test in patients with autosomal dominant polycystic kidney disease. Scand J Clin Lab Invest. 2010; 70: 561–567. doi: 10.3109/00365513.2010.527012.
122.
Kluth O, Stadion M, Gottmann P, et al. Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans. Cell Rep. 2019; 26(11):3027–3036.e3. doi: 10.1016/j.celrep.2019.02.056.
123.
Grarup N, Moltke I, Andersen MK, et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nat Genet. 2018; 50(2):172–174. doi: 10.1038/s41588-017-0022-7.
124.
Censin JC, Nowak C, Cooper N, et al. Childhood adiposity and risk of type 1 diabetes: A Mendelian randomization study. PLoS Med. 2017; 14(8):e1002362. Published 2017 Aug 1. doi: 10.1371/journal.pmed.1002362.
125.
Gerdes JM, Christou-Savina S, Xiong Y, et al. Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents. Nat Commun 2014; 5:5308. Published 2014 Nov 6. doi: 10.1038/ncomms6308.
126.
Ostenson CG, Efendic S. Islet gene expression and function in type 2 diabetes; studies in the Goto-Kakizaki rat and humans. Diabetes Obes Metab 2007; 9 Suppl 2:180–186. doi: 10.1111/j.1463-1326.2007.00787.x.
127.
Zimmerman K, Yoder BK. SnapShot: Sensing and Signaling by Cilia. Cell. 2015; 161(3):692–692.e1. doi: 10.1016/j.cell.2015.04.015
128.
Volta F, Scerbo MJ, Seelig A, et al. Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing [published correction appears in Nat Commun. 2021 Aug 3; 12(1):4796. doi: 10.1038/s41467-021-24865-4]. Nat Commun. 2019; 10: 5686. doi: 10.1038/s41467-019-12953-5.
129.
Hughes JW, Cho JH, Conway HE, et al. Primary cilia control glucose homeostasis via islet paracrine interactions. Proc Natl Acad Sci U S A 2020; 117: 8912–8923. doi: 10.1073/pnas.2001936117.
130.
Sundström L, Myhre S, Sundqvist M, et al. The acute glucose lowering effect of specific GPR120 activation in mice is mainly driven by glucagon-like peptide 1. PLoS One 2017; 12: e0189060. doi: 10.1371/journal.pone.0189060
131.
Jin D, Ni TT, Sun J, et al. Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport. Nat Cell Biol 2014; 16: 841–851. doi: 10.1038/ncb3029.
132.
Carboneau BA, Allan JA, Townsend SE, Kimple ME, Breyer RM, Gannon M. Opposing effects of prostaglandin E2 receptors EP3 and EP4 on mouse and human b-cell survival and proliferation. Mol Metab. 2017; 6: 548–559. doi: 10.1016/j.molmet.2017.04.002.
133.
Carboneau BA, Breyer RM, Gannon M. Regulation of pancreatic b-cell function and mass dynamics by prostaglandin signaling. J Cell Commun Signal 2017; 11: 105–116. doi: 10.1007/s12079-017-0377-7.
134.
Robertson RP. Eicosanoids as pluripotential modulators of pancreatic islet function. Diabetes 1988; 37: 367–370. doi: 10.2337/diab.37.4.367.
135.
Rossing P. Diabetic nephropathy: worldwide epidemic and effects of current treatment on natural history. Curr Diab Rep 2006; 6: 479–483. doi: 10.1007/s11892-006-0083-y.
136.
Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 2005; 16 Suppl 1: S30–S33. doi: 10.1681/asn.2004110970.
137.
Kanwar YS, Akagi S, Sun L, et al. Cell biology of diabetic kidney disease. Nephron Exp Nephrol 2005; 101: e100–e110. doi: 10.1159/000087339.
138.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008; 57: 712–717. doi: 10.1016/j.metabol.2008.01.013.
139.
Yin J, Gao Z, Liu D, et al. Berberine improves glucose metabolism through induction of glycolysis. Am J Physiol Endocrinol Metab 2008; 294: E148–E156. doi: 10.1152/ajpendo.00211.2007.
140.
Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006; 55: 2256–2264. doi: 10.2337/db06-0006.
141.
Yin J, Zhang H, Ye J. Traditional Chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets 2008; 8: 99–111. doi: 10.2174/187153008784534330.
142.
Liu WH, Hei ZQ, Nie H, et al. Berberine ameliorates renal injury in streptozotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin Med J (Engl) 2008; 121: 706–712.
143.
Tang L, Lv F, Liu S, Zhang S. Effect of berberine on expression of transforming growth factor-beta1 and type IV collagen proteins in mesangial cells of diabetic rats with nephropathy. Zhongguo Zhong Yao Za Zhi 2011; 36: 3494–3497.
144.
Xie X, Chang X, Chen L, et al. Berberine ameliorates experimental diabetes-induced renal inflammation and fibronectin by inhibiting the activation of RhoA/ROCK signaling. Mol Cell Endocrinol 2013; 381: 56–65. doi: 10.1016/j.mce.2013.07.019.
145.
Domitrović R, Cvijanović O, Pernjak-Pugel E, et al. Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem Toxicol 2013; 62: 397–406. doi: 10.1016/j.fct.2013.09.003.
146.
Yang Y, Ni W, Cai M, Tang L, Wei W. The renoprotective effects of berberine via the EP4-Gαs-cAMP signaling pathway in different stages of diabetes in rats. J Recept Signal Transduct Res 2014; 34: 445–455. doi: 10.3109/10799893.2014.917324147.
147.
Wang X, Yao B, Wang Y, et al. Macrophage Cyclooxygenase-2 Protects Against Development of Diabetic Nephropathy. Diabetes 2017; 66: 494–504. doi: 10.2337/db16-0773.
148.
Chang J, Vacher J, Yao B, et al. Prostaglandin E receptor 4 (EP4) promotes colonic tumorigenesis. Oncotarget 2015; 6: 33500–33511. doi: 10.18632/oncotarget.5589.
149.
Bohle A, Wehrmann M, Bogenschütz O, et al. The pathogenesis of chronic renal failure in diabetic nephropathy. Investigation of 488 cases of diabetic glomerulosclerosis. Pathol Res Pract 1991; 187: 251–259. doi: 10.1016/s0344-0338(11)80780-6.
150.
Woroniecka KI, Park AS, Mohtat D, et al. Transcriptome analysis of human diabetic kidney disease. Diabetes 2011; 60: 2354–2369. doi: 10.2337/db10-1181.
151.
Mohamed R, Jayakumar C, Ramesh G. Chronic administration of EP4-selective agonist exacerbates albuminuria and fibrosis of the kidney in streptozotocin-induced diabetic mice through IL-6. Lab Invest 2013; 93: 933–945. doi: 10.1038/labinvest.2013.85.
152.
Gao M, Cao R, Du S, et al. Disruption of prostaglandin E2 receptor EP4 impairs urinary concentration via decreasing aquaporin 2 in renal collecting ducts. Proc Natl Acad Sci U S A 2015; 112: 8397–8402. doi: 10.1073/pnas.1509565112.
153.
Rojek A, Füchtbauer EM, Kwon TH, et al. Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proc Natl Acad Sci U S A 2006; 103: 6037–6042. doi: 10.1073/pnas.0511324103.
154.
Nielsen S, DiGiovanni SR, Christensen EI, et al. Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci U S A 1993; 90: 11663–11667. doi: 10.1073/pnas.90.24.11663.
155.
Qi Z, Cai H, Morrow JD, Breyer MD. Differentiation of cyclooxygenase 1- and 2-derived prostanoids in mouse kidney and aorta. Hypertension 2006; 48: 323–328. doi: 10.1161/01.HYP.0000231934.67549.b7.
156.
Nathan DM, McGee P, Steffes MW, Lachin JM; DCCT/EDIC Research Group. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes 2014; 63: 282–290. doi: 10.2337/db13-0782.
157.
Kanter JE, Kramer F, Barnhart S, et al. Diabetes promotes an inflammatory macrophage phenotype and atherosclerosis through acyl-CoA synthetase 1. Proc Natl Acad Sci U S A 2012; 109: E715–E724. doi: 10.1073/pnas.1111600109.
158.
Shao S, He F, Yang Y, et al. Th17 cells in type 1 diabetes. Cell Immunol 2012; 280:16–21. doi: 10.1016/j.cellimm.2012.11.001.159.
159.
Padmos RC, Hillegers MH, Knijff EM, et al. A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes. Arch Gen Psychiatry 2008; 65: 395–407. doi: 10.1001/archpsyc.65.4.395.
160.
Devaraj S, Glaser N, Griffen S, et al. Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 2006; 55: 774–779. doi: 10.2337/diabetes.55.03.06.db05-1417.
161.
Wen Y, Gu J, Li SL, et al. Elevated glucose and diabetes promote interleukin-12 cytokine gene expression in mouse macrophages. Endocrinology 2006; 147: 2518–2525. doi: 10.1210/en.2005-0519162.
162.
Nagareddy PR, Murphy AJ, Stirzaker RA, et al. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab 2013; 17: 695–708. doi: 10.1016/j.cmet.2013.04.001.
163.
Akaogi J, Yamada H, Kuroda Y, et al. Prostaglandin E2 receptors EP2 and EP4 are up-regulated in peritoneal macrophages and joints of pristane-treated mice and modulate TNF-alpha and IL-6 production. J Leukoc Biol 2004; 76: 227–236. doi: 10.1189/jlb.1203627.
164.
Ma W, Quirion R. Up-regulation of interleukin-6 induced by prostaglandin E from invading macrophages following nerve injury: an in vivo and in vitro study. J Neurochem 2005; 93: 664–673. doi: 10.1111/j.1471-4159.2005.03050.x.
165.
Qian X, Zhang J, Liu J. Tumor-secreted PGE2 inhibits CCL5 production in activated macrophages through cAMP/PKA signaling pathway. J Biol Chem 2011; 286: 2111–2120. doi: 10.1074/jbc.M110.154971.
166.
Kawahara K, Hohjoh H, Inazumi T, et al. Prostaglandin E2-induced inflammation: Relevance of prostaglandin E receptors. Biochim Biophys Acta 2015; 1851: 414–421. doi: 10.1016/j.bbalip.2014.07.008.
167.
Yokoyama U, Iwatsubo K, Umemura M, et al. The prostanoid EP4 receptor and its signaling pathway. Pharmacol Rev. 2013; 65: 1010–1052. doi: 10.1124/pr.112.007195.
168.
Kalinski P. Regulation of immune responses by prostaglandin E2. J Immunol 2012; 188: 21–28. doi: 10.4049/jimmunol.1101029.
169.
Chen SS, Jenkins AJ, Majewski H. Elevated plasma prostaglandins and acetylated histone in monocytes in Type 1 diabetes patients. Diabet Med 2009; 26: 182–186. doi: 10.1111/j.1464-5491.2008.02658.x.
170.
Esmatjes E, Levy I, Gaya J, Rivera F. Renal excretion of prostaglandin E2 and plasma renin activity in type I diabetes mellitus: relationship to normoglycemia achieved with artificial pancreas. Diabetes Care 1987; 10: 428–431. doi: 10.2337/diacare.10.4.428.
171.
Jia Z, Sun Y, Liu S, et al. COX-2 but not mPGES-1 contributes to renal PGE2 induction and diabetic proteinuria in mice with type-1 diabetes. PLoS One 2014; 9: e93182. doi: 10.1371/journal.pone.0093182.
172.
Chase HP, Williams RL, Dupont J. Increased prostaglandin synthesis in childhood diabetes mellitus. J Pediatr 1979; 94: 185–189. doi: 10.1016/s0022-3476(79)80819-7.
173.
Axelrod L, Shulman GI, Blackshear PJ, et al. Plasma level of 13,14-dihydro-15-keto-PGE2 in patients with diabetic ketoacidosis and in normal fasting subjects. Diabetes 1986; 35: 1004–1010. doi: 10.2337/diab.35.9.1004.
174.
Vallerie SN, Kramer F, Barnhart S, et al. Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes. PLoS One 2016; 11: e0158316. doi: 10.1371/journal.pone.0158316.
175.
Ståhle E, Tammelin A, Bergström R, et al. Sternal wound complications – incidence, microbiology and risk factors. Eur J Cardiothorac Surg 1997; 11: 1146–1153. doi: 10.1016/s1010-7940(97)01210-4.
176.
Sharma R, Puri D, Panigrahi BP, Virdi IS. A modified parasternal wire technique for prevention and treatment of sternal dehiscence. Ann Thorac Surg 2004; 77: 210–213. doi: 10.1016/s0003-4975(03)01339-0.
177.
Yoshida K, Oida H, Kobayashi T, et al. Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation. Proc Natl Acad Sci U S A 2002; 99: 4580–4585. doi: 10.1073/pnas.062053399.
178.
Chung AS, Ferrara N. Developmental and pathological angiogenesis. Annu Rev Cell Dev Biol 2011; 27: 563–584. doi: 10.1146/annurev-cellbio-092910-154002.
179.
Reynolds JD. Insights in ROP. Am Orthopt J 2014; 64: 43–53. doi: 10.3368/aoj.64.1.43.
180.
Fong DS, Aiello LP, Ferris FL 3rd, Klein R. Diabetic retinopathy. Diabetes Care 2004; 27: 2540–2553. doi: 10.2337/diacare.27.10.2540.
181.
Laouri M, Chen E, Looman M, Gallagher M. The burden of disease of retinal vein occlusion: review of the literature. Eye (Lond) 2011; 25: 981–988. doi: 10.1038/eye.2011.92.
182.
Laatikainen L, Ojamo M, Rudanko SL, et al. Improving visual prognosis of the diabetic patients during the past 30 years based on the data of the Finnish Register of Visual Impairment. Acta Ophthalmol 2016; 94: 226–231. doi: 10.1111/aos.12952.
183.
Capra V, Bäck M, Angiolillo DJ, et al. Impact of vascular thromboxane prostanoid receptor activation on hemostasis, thrombosis, oxidative stress, and inflammation. J Thromb Haemost 2014; 12: 126–137. doi: 10.1111/jth.12472.
184.
Xia S, Ma J, Bai X, et al. Prostaglandin E2 promotes the cell growth and invasive ability of hepatocellular carcinoma cells by upregulating c-Myc expression via EP4 receptor and the PKA signaling pathway. Oncol Rep 2014; 32: 1521–1530. doi: 10.3892/or.2014.3393.
185.
Buchanan FG, Wang D, Bargiacchi F, DuBois RN. Prostaglandin E2 regulates cell migration via the intracellular activation of the epidermal growth factor receptor. J Biol Chem 2003; 278: 35451–35457. doi: 10.1074/jbc.M302474200.
186.
Tan S, Chen X, Xu M, et al. PGE2 /EP4 receptor attenuated mucosal injury via β-arrestin1/Src/EGFR-mediated proliferation in portal hypertensive gastropathy. Br J Pharmacol 2017; 174: 848–866. doi: 10.1111/bph.13752.
187.
Ansari KM, Rundhaug JE, Fischer SM. Multiple signaling pathways are responsible for prostaglandin E2-induced murine keratinocyte proliferation. Mol Cancer Res 2008; 6: 1003–1016. doi: 10.1158/1541-7786.MCR-07-2144.
188.
Moran AE, Hunt DH, Javid SH, et al. Apc deficiency is associated with increased Egfr activity in the intestinal enterocytes and adenomas of C57BL/6J-Min/+ mice. J Biol Chem 2004; 279: 43261–43272. doi: 10.1074/jbc.M404276200.
189.
Mouradian M, Kikawa KD, Johnson ED, et al. Key roles for GRB2-associated-binding protein 1, phosphatidylinositol-3-kinase, cyclooxygenase 2, prostaglandin E2 and transforming growth factor alpha in linoleic acid-induced upregulation of lung and breast cancer cell growth. Prostaglandins Leukot Essent Fatty Acids 2014; 90: 105–115. doi: 10.1016/j.plefa.2013.12.001.
190.
Xie T, Zhang Z, Cui Y, et al. Prostaglandin E2 promotes pathological retinal neovascularisation via EP4R-EGFR-Gab1-AKT signaling pathway. Exp Eye Res 2021; 205: 108507. doi: 10.1016/j.exer.2021.108507