Volume 8, Issue 3, May 2020, Page: 101-106
The Effect of Experimental Periodontitis on the Serum Levels of Leptin and IL-18 in Insulin-Treated Diabetic Rats
Eudoxie Pepelassi, Department of Periodontology, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece
Ioanna Xynogala, Department of Periodontology, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece
Despina Perrea, Laboratory for Experimental Surgery & Surgical Research “N. S. Christeas”, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Alkistis Pantopoulou, Laboratory for Experimental Surgery & Surgical Research “N. S. Christeas”, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
George Agrogiannis, 1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
Ioannis Vrotsos, Department of Periodontology, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece
Received: Mar. 8, 2020;       Accepted: Apr. 3, 2020;       Published: Apr. 30, 2020
DOI: 10.11648/j.ajim.20200803.12      View  46      Downloads  36
Abstract
The aim of this study in rats was to assess the effect of ligature-induced periodontitis on insulin-treated type 1 diabetes in terms of serum levels of leptin and interleukin-18 (IL-18). Twenty five male Wistar rats were studied, out of 40 initially used: (1) 14 rats with insulin-treated diabetes (control, DI) and (2) 11 rats with combination of insulin-treated diabetes and periodontitis (test, DIP). For all rats, type 1 diabetes was streptozotocin-induced and insulin treatment started on day 5. For DIP group, periodontitis was induced by ligation on day 16. Serum levels of leptin and IL-18 were assessed on days 16 (baseline) and 77 (final) by using multiplex immunoassay. All rats were sacrificed on day 77 (end of the study). Insulin treatment in the newly-induced diabetes significantly increased serum leptin levels and significantly reduced serum IL-18 levels. In the newly-induced diabetes, the combination of the continuation of insulin treatment and periodontitis non-significantly increased serum leptin and IL-18 levels. Serum IL-18 levels were significantly higher for the combination of periodontitis and insulin-treated diabetes as compared to insulin-treated diabetes alone. Within its limits, this study in rats showed that experimental periodontitis induced changes in serum biomarker levels suggestive of alterations in the systemic inflammation generated by insulin-treated type 1 diabetes.
Keywords
Diabetes Mellitus, Type 1, Insulin, Periodontitis, Interleukin-18, Leptin, Biologic Markers
To cite this article
Eudoxie Pepelassi, Ioanna Xynogala, Despina Perrea, Alkistis Pantopoulou, George Agrogiannis, Ioannis Vrotsos, The Effect of Experimental Periodontitis on the Serum Levels of Leptin and IL-18 in Insulin-Treated Diabetic Rats, American Journal of Internal Medicine. Vol. 8, No. 3, 2020, pp. 101-106. doi: 10.11648/j.ajim.20200803.12
Copyright
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
American Diabetes Association Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37 (Suppl. 1): S81-S90.
[2]
Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018; 89 (Suppl 1): S173–S182.
[3]
Sanz M, Ceriello A, Buysschaert M, Chapple I, Demmer RT, Graziani F et al. Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology. J Clin Periodontol. 2018; 45: 138–149.
[4]
Chapple ILC, Genco R and on behalf of working group 2 of the joint EFP/AAP workshop. Diabetes and periodontal diseases: consensus report of the Joint EFP/ AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol. 2013; 40 (Suppl. 14): S106–S112.
[5]
Landman RE, Puder JJ, Xiao E, Freda PU, Ferin M, Warldaw SL. Endotoxin stimulates leptin in the human and nonhuman primate. J Clin Endocrinol Metab. 2003; 88 (3): 1285-1291.
[6]
Iikuni N, Lam QLK, Lu L, Matarese G, La Cava A. Leptin and Inflammation. Curr Immunol Rev. 2008; 4 (2): 70–79.
[7]
Targońska-Stepniak B, Majdan M, Dryglewska M. Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity. Rheumatol Int. 2008; 28: 585-591.
[8]
Deschner J, Eick S, Damanaki A, Nokhbehsaim M. The role of adipokines in periodontal infection and healing. Mol Oral Microbiol. 2014; 29 (6): 258-269.
[9]
Zhu J, Guo B, Gan X, Zhang L, He Y, Liu B et al. Association of circulating leptin and adiponectin with periodontitis: a systematic review and meta-analysis. BMC Oral Health. 2017; 17 (1): 104-118.
[10]
Zekeridou A, Mombelli A, Cancela J, Courvoisier D, Giannopoulou C. Systemic inflammatory burden and local inflammation in periodontitis: What is the link between inflammatory biomarkers in serum and gingival crevicular fluid? Clin Exp Dent Res. 2019; 5 (2): 128–135.
[11]
Soliman AT, Omar M, Assem HM, Nasr IS, Rizk MM, Matary WEI et al. Serum leptin concentrations in children with type 1 diabetes mellitus: relationship to body mass index, insulin dose, and glycemic control. Metabolism. 2002; 51 (3): 292-296.
[12]
Dogan Y, Akarsu S, Ustunday B, Yilmaz E, Gurgoze MK. Serum IL-1beta, IL-2, and IL-6 in insulin dependent diabetic children. Mediators Inflamm. 2006; 1 (59206): 1-6.
[13]
Stechova K, Bohmova K, Vrabelova Z, Sepa A, Stadlerova G, Zacharovova K et al. High T-helper-1 cytokines but low T-helper-3 cytokines, inflammatory cytokines and chemokines in children with high risk of developing type 1 diabetes. Diabetes Metab Res Rev. 2007; 23: 462-471.
[14]
Buduneli N and Kinane DF. Host-derived diagnostic markers related to soft tissue destruction and bone degradation in periodontitis. J Clin Periodontol. 2011; 38 (Suppl 11): 85–105.
[15]
Takeda M, Ojima M, Yoshioka H, Inaba H, Kogo M, Shizukuishi S et al. Relationship of serum advanced glycation end products with deterioration of periodontitis in type 2 diabetes patients. J Periodontol. 2006; 77: 15-20.
[16]
Soliman NA. Effect of experimentally induced diabetes mellitus on serum leptin level and the role of insulin replacement therapy. Egypt J Hosp Med. 2001; 3: 190-208.
[17]
Rothe H, Jenkins NA, Copeland NG, Kolb H. Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near IDD2. J Clin Invest. 1997; 99 (3): 469–474.
[18]
Sánchez-Hernández PE, Zamora-Perez AL, Fuentes-Lerma M, Robles-Gómez C, Mariaud-Schmidt RP, Guerrero-Velázquez C. IL-12 and IL-18 levels in serum and gingival tissue in aggressive and chronic periodontitis. Oral Dis. 2011; 17 (5): 522-529.
[19]
Ghanim H, Korzeniewski K, Sia CL, Abuaysheh S, Lohano T, Chaudhuri A, Dandona P. Suppressive effect of insulin infusion on chemokines and chemokine receptors. Diabetes Care. 2010; 33 (5): 1103-1108.
[20]
Holzhausen M, Garcia DF, Pepato MT and Marcantonio EJr. The influence of short-term diabetes mellitus and insulin therapy on alveolar bone loss in rats. J Periodont Res. 2004; 39 (3): 188-193.
[21]
Cetinkaya BO, Keles GC, Ayas B, Sakallioglu EE and Acikgoz G. The expression of vascular endothelial growth factor in a rat model at destruction and healing stages of periodontal disease. J Periodontol. 2007; 78 (6): 1129-1135.
[22]
Pepelassi E, Xynogala I, Perrea D, Agrogiannis G, Pantopoulou A, Patsouris E et al. Histometric assessment of the effect of diabetes mellitus on experimentally induced periodontitis in rats. J Int Acad Periodontol. 2012; 14 (2): 35-41.
[23]
Xynogala I, Pepelassi E, Perrea D, Agrogiannis G, Pantopoulou A, Patsouris E et al. Adiponectin and interleukin-6 levels in insulin-treated diabetic rats with experimental periodontitis. Braz Oral Res. 2012; 26 (1): 71-76.
[24]
Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013; Apr 8, doi: 10.3389/fnins.2013.00051.
[25]
Kim GH, Szabo A, King EM, Ayala J, Ayala JE, Altarejos JY. Leptin recruits Creb-regulated transcriptional coactivator 1 to improve hyperglycemia in insulin-deficient diabetes. Mol Metab. 2014; 4 (3): 227-236.
[26]
Denroche HC, Levi J, Wideman RD, Sequeira RM, Huynh FK, Covey SD et al. Leptin therapy reverses hyperglycemia in mice with streptozotocin-induced diabetes, independent of hepatic leptin signaling. Diabetes. 2011; 60 (5): 1414-1423.
[27]
Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H, Sugita N, Yoshie H. The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. J Periodontol. 2010; 81 (8): 1118-1123.
[28]
Karthikeyan BV and Pradeep AR. Gingival crevicular fluid and serum leptin: their relationship to periodontal health and disease. J Clin Periodontol. 2007; 34 (6): 467-472.
[29]
Altinova AE, Yetkin I, Akbay E, Bukan N, Arslan M. Serum IL-18 levels in patients with type 1 diabetes: relations to metabolic control and microvascular complications. Cytokine. 2008; 42 (2): 217-221.
[30]
Ryba-Stanisławowska M, Rybarczyk-Kapturska K, Myśliwiec M, Myśliwska J. Elevated Levels of Serum IL-12 and IL-18 are Associated with Lower Frequencies of CD4+ CD25highFOXP3+ Regulatory T cells in Young Patients with Type 1 Diabetes. Inflammation. 2014; 37 (5): 1513–1520.
[31]
Harms RZ, Yarde DN, Guinn Z, Lorenzo-Arteaga KM, Corley KP, Cabrera MS et al. Increased expression of IL-18 in the serum and islets of type 1 diabetics. Mol Immunol. 2015; 64 (2): 306-312.
[32]
Nicoletti F, Conget I, Di Marco R, Speciale AM, Morìnigo R, Bendtzen K et al. Serum levels of the interferon-gamma-inducing cytokine interleukin-18 are increased in individuals at high risk of developing type 1 diabetes. Diabetologia. 2001; 44 (3): 309-311.
[33]
Schallhorn RA, Patel DN, Chandrasekar B, Mealey BL. Periodontal disease in association with systemic levels of Interleukin-18 and CXC ligand 16 in patients undergoing cardiac catheterization. J Periodontol. 2010; 81 (8): 1180-1186.
[34]
Orozco A, Gemmell E, Bickel M, Seymour GJ. Interleukin-1beta, interleukin-12 and interleukin-18 levels in gingival fluid and serum of patients with gingivitis and periodontitis. Oral Microbiol Immunol. 2006; 21 (4): 256-260.
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