Vitamin D suppresses inflammatory responses in insulin resistance

Rona Kartika(1*), Heri Wibowo(2)

(1) Master Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia
(2) Parasitology Department, Faculty of Medicine, Universitas Indonesia
(*) Corresponding Author



Vitamin D has been known as a vitamin for bone health and mineral homeostasis. However, since the discovery of vitamin D receptor (VDR) in various types of cell, that statement has changed. Immune cells are known to express VDR and enzyme 1α-hydroxylase that could convert vitamin D into its active form, 1.25 dihydroxyvitamin D. In immune cells, vitamin D works as an immunomodulator which affects various levels of immune response. The net effects of vitamin D are increasing mucosal immunity, but dampening the adaptive immune system. Vitamin D deficiency is commonly found in people with diabetes mellitus (DM) and obesity. It is also associated with increased insulin resistance and poor glucose control. This review will explain how vitamin D as immunomodulator dampens insulin resistance. In immune cells from subjects with insulin resistance, administration of vitamin D could reduce the expression of pro-inflammatory cytokines through the NF-κB and MAPK pathways, thus the levels of pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6 are decreased. The same thing happens in preadipocytes and mature adipocytes cells. In these cells, vitamin D suppresses the expression of pro-inflammatory mediators such as IL-6 and MCP-1. Although in the invitro studies, the administration of vitamin D showed a promising effect in modulating the immune system, the clinical effect of vitamin D supplementation in reducing insulin resistance in individuals with type 2 DM (T2DM) and prediabetes is still inconclusive



vitamin D; inflammation; insulin resistance; diabetes mellitus; cytokines;

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  1. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients 2013; 5(7):2502-21.
  2. Hewison M. Symposium 3: Vitamin D and immune function: from pregnancy to adolescence. Vitamin D and immune function: an overview. Proceeding of the Nutrition Society 2012; 71:50-61
  3. Aranow C. Vitamin D and the immune system. J Investig Med 2011; 59(6):881-6.
  4. Vanlint S. Vitamin D and obesity. Nutrients 2013; 5(3):949-56.
  5. Lips P, Eekhoff M, van Schoor N, Oosterwerff M, de Jongh R, Krul-Poel Y, et al. Vitamin D and type 2 diabetes. J Steroid BiochemMolBiol 2017; 173:280-5.
  6. Calvo-Romero JM, Ramiro-Lozano JM. Vitamin D levels in patients with type 2 diabetes mellitus. J Investig Med 2015; 63(8):921-3.
  7. Scragg R, Sowers MF, Bell C. Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 2004; 27(12):2813-8.
  8. Wootton AM. Improving the measurement of 25-hydroxyvitamin D. ClinBiochem Rev 2005; 26(1):33-6.
  9. Holick MF. Vitamin D deficiency. N Eng J Med 2007; 257(3):266-81.
  10. Sung CC, Liao MT, Lu KC, Wu CC. Role of vitamin D in insulin resistance. J Biomed Biotechnol 2012; 2012:634195.
  11. Oliver M, Spelmink L, Hiew J, Meyer-Hoffert U, Henriques-Normark B, Bergman P. Immunomodulatory effects of vitamin D on innate and adaptive immune responses to Streptococcus pneumonia. J Infect Dis 2013; 208(9):1474-81.
  12. Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C. Vitamin D: Modulator of the immune system. CurrOpinPharmacol2010; 10(4):482-96.
  13. Cantorna MT. Mechanisms underlying the effect of vitamin D on the immune system. Proc NutrSoc 2011; 69(3):286-9.
  14. Chun RF. New perspectives on the vitamin D binding protein. Cell BiochemFunct 2012; 30(6):445-56.
  15. Hewison M. Vitamin D and nnnate and adaptive immunity. VitamHorm 2011; 86:23-62.
  16. Chen L, Chen R, Wang H, Liang F. Mechanisms linking inflammation to insulin resistance. Int J Endocrino 2015;2015:508409.
  17. Mohiuddin SS. Low grade chronic inflammatory response in pathogenicity of diabetes mellitus. Curre Res Diabetes Obes J 2018; 5(4):1-6.
  18. Rehman K, Akash MS. Mechanisms of inflammatory responses and development of insulin resisance: how are they interlinked? J Biomed Sci2016; 23(1):87.
  19. Zeng C, Shi X, Zhang B, Liu H, Zhang L, Ding W, et al. The imbalance of Th17/Th1/Tregs in patients with type 2 diabetes: relationship with metabolic factors and complications. J Mol Med 2012; 90(2):175-86.
  20. Hewison M. Vitamin D and the immune system: new perspectives on an old theme. EndocrinolMetabClin North Am 2010; 39(2):365-79.
  21. Cohen-Lahav M, Shany S, Tobvin D, Chaimovitz C, Douvdevani A. Vitamin D decreases NFκB activity by increasing IκB α levels. Nephrol Dial Transplant 2006; 21(4):889-97.
  22. Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC. Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκBkinas Beta protein. J BiolChem 2013; 288(27):19450-8.
  23. Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 2012; 188(5):2127-35.
  24. Sterling KA, Eftekhari P, Girndt M, Kimmel PL, Raj DS. The immunoregulatory function of vitamin D: implication in chronic kidney disease. Nat Rev Nephrol 2012; 8(7):403-12.
  25. Hayes CE, Hubler SL, Moore JR, Barte LE, Praska CE, Nashold FE. Vitamin D actions on CD4+ T cells in autoimmune disease. Front Immunol 2015; 6:100.
  26. de Souza WN, Martini LA. The role of vitamin D in obesity and inflammation at adipose tissue. J ObesMetab Res 2015; 2(3):161-6.
  27. Ching S, Kashinkunti S, Niehaus MD, Zinser GN. Mammary adiposities bioactivate 25-hydroxyvitamin D3 and signal via Vitamin D receptor, modulating mammary epithelial cell growth. J Cell Biochem 2011; 112:3393-405.
  28. Gao D, Trayhurn P, Bing C. 1.25 - Dihydroxyvitamin D3 inhibits the cytokine-induced secretion of MCP-1 and reduces monocyte recruitment by human preadipocytes. Int J Obes 2013; 37(3):357-65.
  29. Ding C, Wilding JP, Bing C. 1.25 Dihydroxyvitamin D3 protects against macrophage-induced activation of NFKB and MAPK signaling and chemokine release in human adipocytes. PLoS One 2013; 8:61707.
  30. Mutt SJ, Karhu T, Lehtonen S, Lehenkari P, Carlberg C, Saarnio J, et al. Inhibition of cytokine secretion from adipocytes by 1,25-dihydroxyvitamin D3 via NF-κB pathway. FASEB J 2012; 26(11):4400-7.
  31. Wu C, Qiu S, Zhu X, Li L. Vitamin D supplementation and glycemic control in type 2 diabetes patients: A systematic review and meta-analysis. Metabolism 2017; 73:67-76.
  32. He S, Yu S, Zhou Z, Wang C, Wu Y, Li W. Effect of vitamin D supplementation on fasting plasma glucose, insulin resistance, and prevention of type 2 diabetes mellitus in non-diabetics: A systematic review and meta-analysis. Biomed Rep 2018; 8(5):475-84.
  33. Hoseini SA, Aminorroaya A, Iraj B, Amini M. The effects of oral vitamin D on insulin resistance n pre-diabetic patients. J Res Med Sci 2013; 18(1):47-51.


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