Obezite, Tip 2 Diyabet ve İnsülin Direnci Arasındaki Bağlantı: İnflamasyon

Year 2018, Volume: 1 Issue: 2, 27 - 36, 15.10.2018

Cansu Özbayer Emine Yağcı , Hülyam Kurt

Abstract

Tip 2 Diabetes Mellitus (T2DM), obezite ve fiziksel inaktiviteye bağlı olarak sıklıkla gözlemlenen,

periferik dokularda insülin direnci ve pankreatik β hücresi disfonksiyonu ile karakterize olan

kronik metabolik bir hastalıktır. İnsülin direnci, pankreas tarafından salgılanan insülinin yağ,

kas ve karaciğer hücrelerinde gerekli veya yeterli tepkiyi oluşturamaması durumudur. Obezite,

sıklıkla insülin direnci ve T2DM’nin de eşlik ettiği yağ dokunun aşırı artışıyla karakterize

metabolik bir hastalıktır. Yağ doku nedenli inflamasyon da, obezite ve insülin direncini birbirine

bağlar ve böylece T2DM’nin erken evresinde anahtar rol oynar. İnflamasyon, immün sistemin

doğal bir bileşeni olup, her türlü zararlı, yabancı ve yıkıcı etkene karşı organizmanın verdiği

doğal savunma yanıtıdır. Ancak inflamasyon, kişinin kendi dokularına karşı geliştiğinde,

yeterince kontrol edilemediği durumlarda veya kronik inflamasyon geliştiğinde diyabet, obezite

ve kanserin de içinde bulunduğu çeşitli patolojiler ortaya çıkmaktadır. İnflamasyon mekanizması;

interlökinler, interferonlar, TNF-α, MAP-kinazlar, Toll-like reseptörler, NF-kB gibi kemokin,

kemokin reseptörleri ve sitokinlerden oluşan çok sayıda anahtar düzenleyiciyi içerir.

İnflamasyonun, insülin direnci üzerine olan önemli etkisi bilinmekle birlikte günümüzde

inflamasyonun T2DM ve obezite üzerine etkisi henüz aydınlatılamamıştır. Derlememizde

insülin direnci, obezite, T2DM hastalıklarının inflamasyonla ilişkisi incelenecek ve inflamatuvar

süreçte görev alan temel genler ayrıntılı olarak ele alınacaktır.

Keywords

Tip 2 diyabet, Obezite, İnflamasyon, İnsülin direnci

References

• 1. Aguiree F, Brown A, Cho NH, et al. IDF diabetes atlas. 2013. 2.Malnick SD, Knobler H. The medical complications of obesity. Qjm 2006; 99(9): 565-79. 3. Satman I, Yilmaz T, Sengül A, et al. Populationbased study of diabetes and risk characteristics in Turkey. Diabetes Care 2002; 25(9): 1551-6. 4. Satman I, Omer B, Tutuncu Y, et al. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. European journal of epidemiology 2013; 28(2): 169-80. 5. Wang Y, Zhong J, Zhang X, et al. The Role of HMGB1 in the Pathogenesis of Type 2 Diabetes. Journal of Diabetes Research 2016. 6. Burtis CA, Ashwood ER, Bruns DE. Tietz fundamentals of clinical chemistry. 5th Ed. Philadelphia: WB Saunders, 2001.1091 pp. 7. Katz MJ, Ness SM. Diabetes Mellitus, Type 2. Wild iris Medical Education Available at: wildirismedicaleducation.com 8. Özbayer C, Kurt H, Yangı B. TLR4 ve TLR4 Sinyal Yolağındaki Genetik Varyantların İnsülin Direnci ve Diyabet Riski İle İlişkisi. Journal of Clinical and Analytical Medicine 2014; 5(2): 168- 72. 9. Ginter E, Simko V. Type 2 diabetes mellitus, pandemic in 21st century. Diabetes: Springer; 2013. p. 42-50. 10. Donath MY. Targeting inflammation in the treatment of type 2 diabetes: time to start. Nat Rev Drug discov 2014; 13(6): 465-76. 11. Rivas T, Lauro M, Grimes C, et al. Probing the Inflammatory Response Behind Diabetes and Obesity via the Biochemical Characterization of NOD1, an Innate Immune Receptor. The FASEB Journal 2015; 29: 559.40. 12. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. 9th Ed. Elsevier Health Sciences; Illinois: 2012. p928. 13. Şentürk N. Kütanöz inflamasyon. TURKDERM 2013; 47(1): 28-36. 14. Xu H, Barnes GT, Yang Q, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. The Journal of clinical investigation 2003; 112(12): 1821-30. 15. Shacter E, Weitzman SA. Chronic inflammation and cancer. Oncology (Williston Park, NY). 2002; 16(2): 217-26, 29; discussion 30-2. 16. Esser N, Legrand-Poels S, Piette J, et al. Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes research and clinical practice 2014; 105(2): 141-50. 17. Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. Journal of Clinical Investigation 2006; 116(7): 1793. 18. Watanabe Y, Nagai Y, Takatsu K. Activation and regulation of the pattern recognition receptors in obesity-induced adipose tissue inflammation and insulin resistance. Nutrients 2013; 5(9): 3757-78. 19. Godsland IF. Insulin resistance and hyperinsulinaemia in the development and progression of cancer. Clinical Science 2010; 118(5): 315-32. 20. Galic S, Oakhill JS, Steinberg GR. Adipose tissue as an endocrine organ. Molecular and cellular endocrinology 2010; 316(2): 129-39. 21. Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006; 444(7121): 840-6. 22. Massaro M, Scoditti E, Pellegrino M, et al. Therapeutic potential of the dual peroxisome proliferator activated receptor (PPAR) α/γ agonist aleglitazar in attenuating TNF-α-mediated inflammation and insulin resistance in human adipocytes. Pharmacol Res 2016; 107: 125-36. 23. Dandona P, Ghanim H, Bandyopadhyay A et al. Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans. Diabetes Care 2010; 33(11): 2416-23. 24. Keskin S, Sayalı E, Temeloğlu E et al. Obezite ve inflamasyon. Turkiye Klinikleri Journal of Medical Sciences 2005; 25(5): 636-41. 25. Hancı T, Türkön H, Aydoğdu AÇ et al. Yüksek Duyarlıklı C-reaktif Protein (HSCRP) ve Obezite İlişkisi. Journal of Turkish Clinical Biochemistry 2012; 10: 1-7. 26. Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Res Clin Pract 2005; 69(1): 29-35. 27. Chadt A, Scherneck S, Joost H-G et al. Molecular links between obesity and diabetes: “Diabesity”. Endocrinology Online Book. Available at: http://www.endotext.org/obesity/obesity11/ obesityframe11.htm 28. de Luca C, Olefsky JM. Stressed out about obesity and insulin resistance. Nature Medicine 2006; 12(1): 41-3. 29. Uludağ B. Vücut kitle indeksi ile inflamatuvar parametrelerin ilişkisi. Pamukkale Üniversitesi Tıp Fakültesi Uzmanlık Tezi, 2014. 30. Bastard J-P, Maachi M, Lagathu C et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. European Cytokine Network 2006; 17(1): 4-12. 31.Çağlar M, Kemokinler KE. Kemokin Reseptörleri ve İnflamasyon ANKEM Dergisi 2004; 18: 164-8. 32. Ota T. Chemokine systems link obesity to insulin resistance. Diabetes & Metabolism Journal 2013; 37(3): 165-72. 33. Güneş H. Sitokinlerin hücre döngüsü üzerinde etkileri. Tr J of Biology 1999; 23: 283-92. 34. Eser B, Islimye Taskin M, Hismiogullari AA et al. The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome. Journal of Obstetrics and Gynaecology 2016: 1-5. 35. Wolf JS, Chen Z, Dong G et al. IL (interleukin)- 1α promotes nuclear factor-κB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. Clinical Cancer Research 2001; 7(6): 1812-20. 36. Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine & Growth Factor Reviews 2002; 13(4): 357-68. 37. Ouyang W, Rutz S, Crellin NK, et al. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Ann Rev Immunol 2011; 29: 71-109. 38. Labzin LI, Lauterbach MA, Latz E. Interferons and inflammasomes: Cooperation and counterregulation in disease. J Allergy & Clin Immunol 2016; 138(1): 37-46. 39. Ito R, Shin‐Ya M, Kishida T, et al. Interferongamma is causatively involved in experimental inflammatory bowel disease in mice. Clin & Exp Immunol 2006; 146(2): 330-8. 40. Wang KS, Li J, Wang Z, et al. Artemisinin inhibits inflammatory response via regulating NF-κB and MAPK signaling pathways. Immunopharmacol & Immunotoxicol 2016; 1-9. 41. Lai J-l, Liu Y-h, Liu C, et al. Indirubin inhibits LPS-Induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways. Inflammation 2016; 1-12. 42. Ve T, J Gay N, Mansell A, et al. Adaptors in toll-like receptor signaling and their potential as therapeutic targets. Current Drug Targets 2012; 13(11): 1360-74. 43. Browne EP. Regulation of B‐cell responses by Toll‐like receptors. Immunology 2012; 136(4): 370-9. 44. Drexler SK, Foxwell BM. The role of toll-like receptors in chronic inflammation. The international journal of biochemistry & cell biology 2010; 42(4): 506-18. 45. Kanczkowski W, Ziegler C, Zacharowski K, et al. Toll-like receptors in endocrine disease and diabetes. Neuroimmunomodulation 2008; 15(1): 54-60. 46. Tilg H, Moschen AR. Inflammatory mechanisms in the regulation of insulin resistance. Molecular medicine 2008; 14(3-4): 222. 47. Kim JJ, Sears DD. TLR4 and insulin resistance. Gastroenterology research and practice 2010; 2010. 48. Tak PP, Firestein GS. NF-κB: a key role in inflammatory diseases. The Journal of clinical investigation 2001; 107(1): 7-11. 49. Lawrence T. The nuclear factor NF-κB pathway in inflammation. Cold Spring Harbor perspectives in biology 2009; 1(6): a001651.