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A brief review of vitamin D as a potential target for the regulation of blood glucose and inflammation in diabetes-associated periodontitis

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Abstract

Diabetes is a metabolic disorder associated with various complications, including periodontitis. The risk of periodontitis is increased in patients with diabetes, while vitamin D deficiency is associated with both diabetes and periodontitis. Thus, there is a need to identify the molecular effects of vitamin D on the regulation of inflammation and glucose in diabetes-associated periodontitis. The Web of Science, Scopus, and PubMed databases were searched for studies of the molecular effects of vitamin D. Molecular effects were reportedly mediated by salivary secretions, interactions of advanced glycation end products (AGEs) with receptors of AGEs (RAGEs), cytokines, and oxidative stress pathways linking diabetes with periodontitis. Vitamin D supplementation attenuates inflammation in diabetes-associated periodontitis by reducing the levels of inflammatory cytokines and numbers of immune cells; it also has antibacterial effects. Vitamin D reduces cytokine levels through regulation of the extracellular signal-related kinase 1/2 and Toll-like receptor 1/2 pathways, along with the suppression of interleukin expression. Glucose homeostasis is altered in diabetes either because of reduced insulin production or decreased insulin sensitivity. These vitamin D-related alterations of glucoregulatory factors may contribute to hyperglycaemia; hyperglycaemia may also lead to alterations of glucoregulatory factors. This review discusses the pathways involved in glucose regulation and effects of vitamin D supplementation on glucose regulation. Further studies are needed to characterise the effects of vitamin D on diabetes-associated periodontitis.

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References

  1. Association AD (2007) Diagnosis and classification of diabetes mellitus. Diabetes Care 30(Suppl 1):S5–S10. https://doi.org/10.2337/dc07-S042

    Article  CAS  Google Scholar 

  2. Cantley J, Ashcroft FM (2015) Q & amp;A: insulin secretion and type 2 diabetes: why do β-cells fail? BMC Biol 13(1):33. https://doi.org/10.1186/s12915-015-0140-6

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tabish SA (2007) Is diabetes becoming the biggest epidemic of the twenty-first century? Int J Health Sci 1(2):5–8

    Google Scholar 

  4. Sinding SW (2009) Population, poverty and economic development. Philos Trans R Soc B 364(1532):3023–3030. https://doi.org/10.1098/rstb.2009.0145

    Article  Google Scholar 

  5. Chan RSM, Woo J (2010) Prevention of overweight and obesity: how effective is the current public health approach. Int J Environ Res Public Health 7(3):765–783. https://doi.org/10.3390/ijerph7030765

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cade WT (2008) Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 88(11):1322–1335. https://doi.org/10.2522/ptj.20080008

    Article  PubMed  PubMed Central  Google Scholar 

  7. Singh VP, Bali A, Singh N, Jaggi AS (2014) Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol 18(1):1–14. https://doi.org/10.4196/kjpp.2014.18.1.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rask-Madsen C, King GL (2013) Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab 17(1):20–33. https://doi.org/10.1016/j.cmet.2012.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang X, Wang H, Zhang T, Cai L, Kong C, He J (2020) Current knowledge regarding the interaction between oral bone metabolic disorders and diabetes mellitus. Front Endocrinol 11:e00536. https://doi.org/10.3389/fendo.2020.00536

    Article  Google Scholar 

  10. Könönen E, Gursoy M, Gursoy U (2019) Periodontitis: a multifaceted disease of tooth-supporting tissues. J Clin Med 8(8):1135. https://doi.org/10.3390/jcm8081135

    Article  CAS  PubMed Central  Google Scholar 

  11. Shaju JP, Zade RM, Das M (2011) Prevalence of periodontitis in the Indian population: a literature review. J Indian Soc Periodontol 15(1):29–34. https://doi.org/10.4103/0972-124X.82261

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lee J-H, Oh J-Y, Youk T-M, Jeong S-N, Kim Y-T, Choi S-H (2017) Association between periodontal disease and non-communicable diseases: a 12-year longitudinal health-examinee cohort study in South Korea. Medicine 96(26):e7398. https://doi.org/10.1097/MD.0000000000007398

    Article  PubMed  PubMed Central  Google Scholar 

  13. Sanz M, Marco del Castillo A, Jepsen S et al (2020) Periodontitis and cardiovascular diseases: consensus report. J Clin Periodontol 47(3):268–288. https://doi.org/10.1111/jcpe.13189

    Article  PubMed  PubMed Central  Google Scholar 

  14. Konkel JE, O’Boyle C, Krishnan S (2019) Distal consequences of oral inflammation. Front Immunol 10:1403. https://doi.org/10.3389/fimmu.2019.01403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Silva N, Abusleme L, Bravo D et al (2015) Host response mechanisms in periodontal diseases. J Appl Oral Sci 23(3):329–355. https://doi.org/10.1590/1678-775720140259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cekici A, Kantarci A, Hasturk H, Van Dyke TE (2000) Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 64(1):57–80. https://doi.org/10.1111/prd.12002

    Article  Google Scholar 

  17. Mohamed AMFS (2008) An overview of bone cells and their regulating factors of differentiation. Malaysian J Med Sci 15(1):4–12

    Google Scholar 

  18. Hanes PJ, Krishna R (2010) Characteristics of inflammation common to both diabetes and periodontitis: are predictive diagnosis and targeted preventive measures possible? EPMA J 1(1):101–116. https://doi.org/10.1007/s13167-010-0016-3

    Article  PubMed  PubMed Central  Google Scholar 

  19. Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R (2019) Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev 16(5):442–449. https://doi.org/10.2174/1573399815666191024085838

    Article  Google Scholar 

  20. Graves DT, Ding Z, Yang Y (2020) The impact of diabetes on periodontal diseases. Periodontol 82(1):214–224. https://doi.org/10.1111/prd.12318

    Article  Google Scholar 

  21. Rhee SY, Kim YS (2018) The role of advanced glycation end products in diabetic vascular complications. Diabetes Metab J 42(3):188–195. https://doi.org/10.4093/dmj.2017.0105

    Article  PubMed  PubMed Central  Google Scholar 

  22. De Oliveira S, Rosowski EE, Huttenlocher A (2016) Neutrophil migration in infection and wound repair: going forward in reverse. Nat Rev Immunol 16(6):378–391. https://doi.org/10.1038/nri.2016.49

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Segal AW (2005) How neutrophils kill microbes. Annu Rev Immunol 23:197–223. https://doi.org/10.1146/annurev.immunol.23.021704.115653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kaplan MJ, Radic M (2012) Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol 189(6):2689–2695. https://doi.org/10.4049/jimmunol.1201719

    Article  CAS  PubMed  Google Scholar 

  25. Rajendran V, Uppoor A (2018) A perspective on NETosis in diabetes and periodontal diseases. J Indian Soc Periodontol 22(4):290–293. https://doi.org/10.4103/jisp.jisp_230_18

    Article  PubMed  PubMed Central  Google Scholar 

  26. Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K (2020) The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Front Immunol 11:1582. https://doi.org/10.3389/fimmu.2020.01582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wong SL, Demers M, Martinod K et al (2015) Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat Med 21(7):815–819. https://doi.org/10.1038/nm.3887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mirza S, Hossain M, Mathews C et al (2012) Type 2-diabetes is associated with elevated levels of TNF-alpha, IL-6 and adiponectin and low levels of leptin in a population of Mexican Americans: a cross-sectional study. Cytokine 57(1):136–142. https://doi.org/10.1016/j.cyto.2011.09.029

    Article  CAS  PubMed  Google Scholar 

  29. Yang M-L, Sodré FMC, Mamula MJ, Overbergh L (2021) Citrullination and PAD enzyme biology in type 1 diabetes—regulators of inflammation, autoimmunity, and pathology. Front Immunol 12:678953. https://doi.org/10.3389/fimmu.2021.678953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kwon E-J, Ju JH (2021) Impact of posttranslational modification in pathogenesis of rheumatoid arthritis: focusing on citrullination, carbamylation, and acetylation. Int J Mol Sci 22(19):10576. https://doi.org/10.3390/ijms221910576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Preshaw PM, Alba AL, Herrera D et al (2012) Periodontitis and diabetes: a two-way relationship. Diabetologia 55(1):21–31. https://doi.org/10.1007/s00125-011-2342-y

    Article  CAS  PubMed  Google Scholar 

  32. Dhir S, Wangnoo S, Kumar V (2018) Impact of glycemic levels in Type 2 diabetes on periodontitis. Indian J Endocrinol Metab 22(5):672–677. https://doi.org/10.4103/ijem.IJEM_566_17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ohlrich EJ, Cullinan MP, Leichter JW (2010) Diabetes, periodontitis, and the subgingival microbiota. J Oral Microbiol 2(1):5818. https://doi.org/10.3402/jom.v2i0.5818

    Article  Google Scholar 

  34. Artese HPC, Foz AM, Rabelo MDS et al (2015) Periodontal therapy and systemic inflammation in type 2 diabetes mellitus: a meta-analysis. PLoS ONE 10(5):e0128344. https://doi.org/10.1371/journal.pone.0128344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong DT (2009) Saliva as a diagnostic tool for periodontal disease: current state and future directions. Periodontol 50(1):52–64. https://doi.org/10.1111/j.1600-0757.2008.00288.x

    Article  Google Scholar 

  36. Negrato CA, Tarzia O (2010) Buccal alterations in diabetes mellitus. Diabetol Metab Syndr 2(1):3. https://doi.org/10.1186/1758-5996-2-3

    Article  PubMed  PubMed Central  Google Scholar 

  37. Celik D, Kantarci A (2021) Vascular changes and hypoxia in periodontal disease as a link to systemic complications. Pathogens 10(10):1280. https://doi.org/10.3390/pathogens10101280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kaigler D, Cirelli JA, Giannobile WV (2006) Growth factor delivery for oral and periodontal tissue engineering. Expert Opin Drug Deliv 3(5):647–662. https://doi.org/10.1517/17425247.3.5.647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Stadtländer CTK-H (2006) Bacterial adhesion to animal cells and tissues. Microbe Mag 1(12):589–589. https://doi.org/10.1128/microbe.1.589.1

    Article  Google Scholar 

  40. Legrand D (2016) Overview of lactoferrin as a natural immune modulator. J Pediatr 173:S10–S15. https://doi.org/10.1016/j.jpeds.2016.02.071

    Article  CAS  PubMed  Google Scholar 

  41. Lynge Pedersen AM, Belstrøm D (2019) The role of natural salivary defences in maintaining a healthy oral microbiota. J Dent 80:S3–S12. https://doi.org/10.1016/j.jdent.2018.08.010

    Article  CAS  PubMed  Google Scholar 

  42. How KY, Song KP, Chan KG (2016) Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol 7:53. https://doi.org/10.3389/fmicb.2016.00053

    Article  PubMed  PubMed Central  Google Scholar 

  43. Courtois P (2021) Oral peroxidases: from antimicrobial agents to ecological actors (Review). Mol Med Rep 24(1):500. https://doi.org/10.3892/mmr.2021.12139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kany S, Vollrath JT, Relja B (2019) Cytokines in inflammatory disease. Int J Mol Sci 20(23):6008. https://doi.org/10.3390/ijms20236008

    Article  CAS  PubMed Central  Google Scholar 

  45. Papathanasiou E, Conti P, Carinci F, Lauritano D, Theoharides TC (2020) IL-1 superfamily members and periodontal diseases. J Dent Res 99(13):1425–1434. https://doi.org/10.1177/0022034520945209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mogi M, Otogoto J, Ota N, Inagaki H, Minami M, Kojima K (1999) Interleukin 1β, interleukin 6, β2-microglobulin, and transforming growth factor-α in gingival crevicular fluid from human periodontal disease. Arch Oral Biol 44(6):535–539. https://doi.org/10.1016/S0003-9969(99)00020-5

    Article  CAS  PubMed  Google Scholar 

  47. Correa FOB, Gonçalves D, Figueredo CMS, Gustafsson A, Orrico SRP (2008) The short-term effectiveness of non-surgical treatment in reducing levels of interleukin-1β and proteases in gingival crevicular fluid from patients with type 2 diabetes mellitus and chronic periodontitis. J Periodontol 79(11):2143–2150. https://doi.org/10.1902/jop.2008.080132

    Article  CAS  PubMed  Google Scholar 

  48. Harmer D, Falank C, Reagan MR (2019) Interleukin-6 interweaves the bone marrow microenvironment, bone loss, and multiple myeloma. Front Endocrinol 9:788. https://doi.org/10.3389/fendo.2018.00788

    Article  Google Scholar 

  49. Pan W, Wang Q, Chen Q (2019) The cytokine network involved in the host immune response to periodontitis. Int J Oral Sci 11(3):30. https://doi.org/10.1038/s41368-019-0064-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ramadan DE, Hariyani N, Indrawati R, Ridwan RD, Diyatri I (2020) Cytokines and chemokines in periodontitis. Eur J Dent 14(3):483–495. https://doi.org/10.1055/s-0040-1712718

    Article  PubMed  PubMed Central  Google Scholar 

  51. Li F, Yu F, Xu X et al (2017) Evaluation of recombinant human FGF-2 and PDGF-BB in periodontal regeneration: a systematic review and meta-analysis. Sci Rep 7(1):65. https://doi.org/10.1038/s41598-017-00113-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Javed F, Al-Askar M, Al-Rasheed A, Al-Hezaimi K (2011) Significance of the platelet-derived growth factor in periodontal tissue regeneration. Arch Oral Biol 56(12):1476–1484. https://doi.org/10.1016/j.archoralbio.2011.06.020

    Article  CAS  PubMed  Google Scholar 

  53. Yamagishi S, Fukami K, Matsui T (2015) Crosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications. Cardiovasc Diabetol 14(1):2. https://doi.org/10.1186/s12933-015-0176-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Rahal A, Kumar A, Singh V et al (2014) Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int 2014:761264. https://doi.org/10.1155/2014/761264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ramasamy R, Vannucci SJ, Du YSS, Herold K, Yan SF, Schmidt AM (2005) Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology 15(7):16R-28R. https://doi.org/10.1093/glycob/cwi053

    Article  CAS  PubMed  Google Scholar 

  56. Peppa M, Vlassara H (2005) Advanced glycation end products and diabetic complications: a general overview. Hormones 4(1):28–37. https://doi.org/10.14310/horm.2002.11140

    Article  PubMed  Google Scholar 

  57. Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C (2013) Oxidative stress in diabetes: implications for vascular and other complications. Int J Mol Sci 14(11):21525–21550. https://doi.org/10.3390/ijms141121525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Matough FA, Budin SB, Hamid ZA, Alwahaibi N, Mohamed J (2012) The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos Univ Med J 12(1):556–569. https://doi.org/10.12816/0003082

    Article  Google Scholar 

  59. Giugliano D, Ceriello A, Paolisso G (1996) Oxidative stress and diabetic vascular complications. Diabetes Care 19(3):257–267. https://doi.org/10.2337/diacare.19.3.257

    Article  CAS  PubMed  Google Scholar 

  60. Yaribeygi H, Sathyapalan T, Atkin SL, Sahebkar A (2020) Molecular mechanisms linking oxidative stress and diabetes mellitus. Oxid Med Cell Longev 2020:8609213. https://doi.org/10.1155/2020/8609213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Marchetti E, Monaco A, Procaccini L et al (2012) Periodontal disease: the influence of metabolic syndrome. Nutr Metab 9(1):88. https://doi.org/10.1186/1743-7075-9-88

    Article  CAS  Google Scholar 

  62. Sharma M, Pandey R, Saluja D (2018) ROS is the major player in regulating altered autophagy and lifespan in sin-3 mutants of C. elegans. Autophagy 14(7):1239–1255. https://doi.org/10.1080/15548627.2018.1474312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxidants Redox Signal 20(7):1126–1167. https://doi.org/10.1089/ars.2012.5149

    Article  CAS  Google Scholar 

  64. Chang PC, Lim LP (2012) Interrelationships of periodontitis and diabetes: a review of the current literature. J Dent Sci 7(3):272–282. https://doi.org/10.1016/j.jds.2012.02.002

    Article  Google Scholar 

  65. Laird E, Ward M, McSorley E, Strain JJ, Wallace J (2010) Vitamin D and bone health. Potential Mech Nutr 2(7):693–724. https://doi.org/10.3390/nu2070693

    Article  CAS  Google Scholar 

  66. Wang TJ, Pencina MJ, Booth SL et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117(4):503–511. https://doi.org/10.1161/CIRCULATIONAHA.107.706127

    Article  CAS  PubMed  Google Scholar 

  67. Mozos I, Marginean O (2015) Links between Vitamin D deficiency and cardiovascular diseases. Biomed Res Int 2015:109275. https://doi.org/10.1155/2015/109275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Di Rosa M, Malaguarnera M, Nicoletti F, Malaguarnera L (2011) Vitamin D3: a helpful immuno-modulator. Immunology 134(2):123–139. https://doi.org/10.1111/j.1365-2567.2011.03482.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Strange RC (2015) Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome. World J Diabetes 6(7):896. https://doi.org/10.4239/wjd.v6.i7.896

    Article  PubMed  PubMed Central  Google Scholar 

  70. Al-Dabhani K, Tsilidis KK, Murphy N et al (2017) Prevalence of vitamin D deficiency and association with metabolic syndrome in a Qatari population. Nutr Diabetes 7(4):e263–e263. https://doi.org/10.1038/nutd.2017.14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Prietl B, Treiber G, Pieber TR, Amrein K (2013) Vitamin D and immune function. Nutrients 5(7):2502–2521. https://doi.org/10.3390/nu5072502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Penido MGMG, Alon US (2012) Phosphate homeostasis and its role in bone health. Pediatr Nephrol 27(11):2039–2048. https://doi.org/10.1007/s00467-012-2175-z

    Article  PubMed Central  Google Scholar 

  73. Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M (2014) Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol 5:151. https://doi.org/10.3389/fphys.2014.00151

    Article  PubMed  PubMed Central  Google Scholar 

  74. El Jilani MM, Mohamed AA, Ben ZH et al (2015) Association between vitamin D receptor gene polymorphisms and chronic periodontitis among Libyans. Libyan J Med 10(1):26771. https://doi.org/10.3402/ljm.v10.26771

    Article  PubMed  Google Scholar 

  75. Garbossa SG, Folli F (2017) Vitamin D, sub-inflammation and insulin resistance. A window on a potential role for the interaction between bone and glucose metabolism. Rev Endocr Metab Disord 18(2):243–258. https://doi.org/10.1007/s11154-017-9423-2

    Article  CAS  PubMed  Google Scholar 

  76. Sung C-C, Liao M-T, Lu K-C, Wu C-C (2012) Role of Vitamin D in insulin resistance. J Biomed Biotechnol 2012:1–11. https://doi.org/10.1155/2012/634195

    Article  CAS  Google Scholar 

  77. Genco RJ, Borgnakke WS (2013) Risk factors for periodontal disease. Periodontol 62(1):59–94. https://doi.org/10.1111/j.1600-0757.2012.00457.x

    Article  Google Scholar 

  78. Tebben PJ, Singh RJ, Kumar R (2016) Vitamin D-mediated hypercalcemia: mechanisms, diagnosis, and treatment. Endocr Rev 37(5):521–547. https://doi.org/10.1210/er.2016-1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Klec C, Ziomek G, Pichler M, Malli R, Graier WF (2019) Calcium signaling in ß-cell physiology and pathology: a revisit. Int J Mol Sci 20(24):6110. https://doi.org/10.3390/ijms20246110

    Article  CAS  PubMed Central  Google Scholar 

  80. Pittas AG, Lau J, Hu FB, Dawson-Hughes B (2007) Review: the role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 92(6):2017–2029. https://doi.org/10.1210/jc.2007-0298

    Article  CAS  PubMed  Google Scholar 

  81. Chagas CEA, Borges MC, Martini LA, Rogero MM (2012) Focus on vitamin D, inflammation and type 2 diabetes. Nutrients 4(1):52–67. https://doi.org/10.3390/nu4010052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Coussens AK, Martineau AR, Wilkinson RJ (2014) Anti-inflammatory and antimicrobial actions of Vitamin D in combating TB/HIV. Scientifica 2014:1–13. https://doi.org/10.1155/2014/903680

    Article  CAS  Google Scholar 

  83. Fleet JC (2017) The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol 453:36–45. https://doi.org/10.1016/j.mce.2017.04.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Pike JW, Meyer MB, Martowicz ML et al (2010) Emerging regulatory paradigms for control of gene expression by 1,25-dihydroxyvitamin D3. J Steroid Biochem Mol Biol 121(1–2):130–135. https://doi.org/10.1016/j.jsbmb.2010.02.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Pike JW, Meyer MB (2010) The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D3. Endocrinol Metab Clin N Am 39(2):255–269. https://doi.org/10.1016/j.ecl.2010.02.007

    Article  CAS  Google Scholar 

  86. Khammissa RAG, Ballyram R, Jadwat Y, Fourie J, Lemmer J, Feller L (2018) Vitamin D deficiency as it relates to oral immunity and chronic periodontitis. Int J Dent 2018:1–9. https://doi.org/10.1155/2018/7315797

    Article  CAS  Google Scholar 

  87. Khammissa RAG, Fourie J, Motswaledi MH, Ballyram R, Lemmer J, Feller L (2018) The biological activities of Vitamin D and its receptor in relation to calcium and bone homeostasis, cancer, immune and cardiovascular systems, skin biology, and oral health. Biomed Res Int 2018:1–9. https://doi.org/10.1155/2018/9276380

    Article  CAS  Google Scholar 

  88. Anand N, Chandrasekaran S, Rajput N (2013) Vitamin D and periodontal health: current concepts. J Indian Soc Periodontol 17(3):302–308. https://doi.org/10.4103/0972-124X.115645

    Article  PubMed  PubMed Central  Google Scholar 

  89. Zhang JM, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45(2):27–37. https://doi.org/10.1097/AIA.0b013e318034194e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Hoare A, Soto C, Rojas-Celis V, Bravo D (2019) Chronic inflammation as a link between periodontitis and carcinogenesis. Mediat Inflamm 2019:1–14. https://doi.org/10.1155/2019/1029857

    Article  CAS  Google Scholar 

  91. Chen L, Deng H, Cui H et al (2018) Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9(6):7204–7218. https://doi.org/10.18632/oncotarget.23208

    Article  PubMed  Google Scholar 

  92. Vijay K (2018) Toll-like receptors in immunity and inflammatory diseases: past, present, and future. Int Immunopharmacol 59:391–412. https://doi.org/10.1016/j.intimp.2018.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Medrano M, Carrillo-Cruz E, Montero I, Perez-Simon J (2018) Vitamin D: effect on haematopoiesis and immune system and clinical applications. Int J Mol Sci 19(9):2663. https://doi.org/10.3390/ijms19092663

    Article  CAS  PubMed Central  Google Scholar 

  94. Lee GL, Yeh CC, Wu JY et al (2019) TLR2 promotes vascular smooth muscle cell chondrogenic differentiation and consequent calcification via the concerted actions of osteoprotegerin suppression and IL-6-Mediated RANKL induction. Arterioscler Thromb Vasc Biol 39(3):432–445. https://doi.org/10.1161/ATVBAHA.118.311874

    Article  CAS  PubMed  Google Scholar 

  95. Oh J, Riek AE, Darwech I et al (2015) Deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice. Cell Rep 10(11):1872–1886. https://doi.org/10.1016/j.celrep.2015.02.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Chin HM, Lai DK, Falchook GS (2019) Extracellular signal-regulated kinase (Erk) inhibitors in oncology clinical trials. J Immunother Precis Oncol 2(1):10–16. https://doi.org/10.4103/JIPO.JIPO_17_18

    Article  Google Scholar 

  97. Gombart AF (2009) The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol 4(9):1151–1165. https://doi.org/10.2217/fmb.09.87

    Article  CAS  PubMed  Google Scholar 

  98. Kawamoto D, Amado PPL, Albuquerque-Souza E et al (2020) Chemokines and cytokines profile in whole saliva of patients with periodontitis. Cytokine 135:155197. https://doi.org/10.1016/j.cyto.2020.155197

    Article  CAS  PubMed  Google Scholar 

  99. Stadler AF, Angst PDM, Arce RM, Gomes SC, Oppermann RV, Susin C (2016) Gingival crevicular fluid levels of cytokines/chemokines in chronic periodontitis: a meta-analysis. J Clin Periodontol 43(9):727–745. https://doi.org/10.1111/jcpe.12557

    Article  CAS  PubMed  Google Scholar 

  100. Kim J, Amar S (2006) Periodontal disease and systemic conditions: a bidirectional relationship. Odontology 94(1):10–21. https://doi.org/10.1007/s10266-006-0060-6

    Article  PubMed  PubMed Central  Google Scholar 

  101. Ghosh SS, Wang J, Yannie PJ, Ghosh S (2020) Intestinal Barrier dysfunction, LPS translocation, and disease development. J Endocr Soc 4(2):39. https://doi.org/10.1210/jendso/bvz039

    Article  CAS  Google Scholar 

  102. Mariano FS, Sardi JD, Duque C, Hõfling JF, Gonçalves RB (2010) The role of immune system in the development of periodontal disease: a brief review. Rev Odonto Ciência 25(3):300–305. https://doi.org/10.1590/S1980-65232010000300016

    Article  Google Scholar 

  103. Mora JR, Iwata M, Von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8(9):685–698. https://doi.org/10.1038/nri2378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Yin K, Agrawal DK (2014) Vitamin D and inflammatory diseases. J Inflamm Res 7(1):69–87. https://doi.org/10.2147/JIR.S63898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC (2013) Vitamin D receptor inhibits nuclear factor κb activation by interacting with IκB kinase β protein. J Biol Chem 288(27):19450–19458. https://doi.org/10.1074/jbc.M113.467670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Slots J (2013) Periodontology: past, present, perspectives. Periodontol 62(1):7–19. https://doi.org/10.1111/prd.12011

    Article  Google Scholar 

  107. Youssef DA, Miller CWT, El-Abbassi AM et al (2011) Antimicrobial implications of vitamin D. Dermatoendocrinol 3(4):220–229. https://doi.org/10.4161/derm.3.4.15027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Botelho J, Machado V, Proença L, Delgado AS, Mendes JJ (2020) Vitamin D deficiency and oral health: a comprehensive review. Nutrients 12(5):1471. https://doi.org/10.3390/nu12051471

    Article  CAS  PubMed Central  Google Scholar 

  109. Szymczak-Pajor I, Śliwińska A (2019) Analysis of association between vitamin D deficiency and insulin resistance. Nutrients 11(4):794. https://doi.org/10.3390/nu11040794

    Article  CAS  PubMed Central  Google Scholar 

  110. Tang H, Li D, Li Y, Zhang X, Song Y, Li X (2018) Effects of vitamin D supplementation on glucose and insulin homeostasis and incident diabetes among nondiabetic adults: a meta-analysis of randomized controlled trials. Int J Endocrinol 2018:1–9. https://doi.org/10.1155/2018/7908764

    Article  CAS  Google Scholar 

  111. Talaei A, Mohamadi M, Adgi Z (2013) The effect of vitamin D on insulin resistance in patients with type 2 diabetes. Diabetol Metab Syndr 5(1):8. https://doi.org/10.1186/1758-5996-5-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Röder PV, Wu B, Liu Y, Han W (2016) Pancreatic regulation of glucose homeostasis. Exp Mol Med 48:e219. https://doi.org/10.1038/emm.2016.6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Wilcox NS, Rui J, Hebrok M, Herold KC (2016) Life and death of β cells in Type 1 diabetes: a comprehensive review. J Autoimmun 71:51–58. https://doi.org/10.1016/j.jaut.2016.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Infante M, Ricordi C, Sanchez J et al (2019) Influence of vitamin D on islet autoimmunity and beta-cell function in type 1 diabetes. Nutrients 11(9):2185. https://doi.org/10.3390/nu11092185

    Article  CAS  PubMed Central  Google Scholar 

  115. Chiu KC, Chuang LM, Lee NP et al (2000) Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level. Metabolism 49(11):1501–1505. https://doi.org/10.1053/meta.2000.17708

    Article  CAS  PubMed  Google Scholar 

  116. Alvarez JA, Ashraf A (2010) Role of vitamin D in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol 2010:1–18. https://doi.org/10.1155/2010/351385

    Article  CAS  Google Scholar 

  117. Chandler PD, Giovannucci EL, Scott JB et al (2015) Effects of vitamin D supplementation on C-peptide and 25-hydroxyvitamin D concentrations at 3 and 6 months. Sci Rep 5(1):10411. https://doi.org/10.1038/srep10411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Nazarian S, St. Peter JV, Boston RC, Jones SA, Mariash CN (2011) Vitamin D3 supplementation improves insulin sensitivity in subjects with impaired fasting glucose. Transl Res 158(5):276–281. https://doi.org/10.1016/j.trsl.2011.05.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Boucher J, Kleinridders A, Kahn CR (2014) Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 6(1):a009191. https://doi.org/10.1101/cshperspect.a009191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Hanke S, Mann M (2009) The phosphotyrosine interactome of the insulin receptor family and its substrates IRS-1 and IRS-2. Mol Cell Proteomics 8(3):519–534. https://doi.org/10.1074/mcp.M800407-MCP200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Huang X, Liu G, Guo J, Su Z (2018) The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci 14(11):1483–1496. https://doi.org/10.7150/ijbs.27173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Schultze SM, Hemmings BA, Niessen M, Tschopp O (2012) PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev Mol Med 14:e1. https://doi.org/10.1017/S1462399411002109

    Article  CAS  PubMed  Google Scholar 

  123. Copps KD, White MF (2012) Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 55(10):2565–2582. https://doi.org/10.1007/s00125-012-2644-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Maestro B, Molero S, Bajo S, Dávila N, Calle C (2002) Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D3. Cell Biochem Funct 20(3):227–232. https://doi.org/10.1002/cbf.951

    Article  CAS  PubMed  Google Scholar 

  125. Szymczak-Pajor I, Drzewoski J, Śliwińska A (2020) The molecular mechanisms by which vitamin d prevents insulin resistance and associated disorders. Int J Mol Sci 21(18):1–34. https://doi.org/10.3390/ijms21186644

    Article  CAS  Google Scholar 

  126. Manna P, Achari AE, Jain SK (2018) 1,25(OH)2-vitamin D3 upregulates glucose uptake mediated by SIRT1/IRS1/GLUT4 signaling cascade in C2C12 myotubes. Mol Cell Biochem 444(1–2):103–108. https://doi.org/10.1007/s11010-017-3235-2

    Article  CAS  PubMed  Google Scholar 

  127. Safarpour P, Daneshi-Maskooni M, Vafa M et al (2020) Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial. BMC Fam Pract 21(1):26. https://doi.org/10.1186/s12875-020-1096-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Manna P, Achari AE, Jain SK (2017) Vitamin D supplementation inhibits oxidative stress and upregulate SIRT1/AMPK/GLUT4 cascade in high glucose-treated 3T3L1 adipocytes and in adipose tissue of high fat diet-fed diabetic mice. Arch Biochem Biophys 615:22–34. https://doi.org/10.1016/j.abb.2017.01.002

    Article  CAS  PubMed  Google Scholar 

  129. Yaribeygi H, Maleki M, Sathyapalan T et al (2020) The molecular mechanisms by which vitamin D improve glucose homeostasis: a mechanistic review. Life Sci 244:117305. https://doi.org/10.1016/j.lfs.2020.117305

    Article  CAS  PubMed  Google Scholar 

  130. Bennett JM, Reeves G, Billman GE, Sturmberg JP (2018) Inflammation–nature’s way to efficiently respond to all types of challenges: implications for understanding and managing “the epidemic” of chronic diseases. Front Med 5:316. https://doi.org/10.3389/fmed.2018.00316

    Article  Google Scholar 

  131. Ye J (2013) Mechanisms of insulin resistance in obesity. Front Med China 7(1):14–24. https://doi.org/10.1007/s11684-013-0262-6

    Article  Google Scholar 

  132. Meghil MM, Hutchens L, Raed A et al (2019) The influence of vitamin D supplementation on local and systemic inflammatory markers in periodontitis patients: a pilot study. Oral Dis 25(5):1403–1413. https://doi.org/10.1111/odi.13097

    Article  PubMed  PubMed Central  Google Scholar 

  133. Pizzino G, Irrera N, Cucinotta M et al (2017) Oxidative stress: harms and benefits for human health. Oxid Med Cell Longev 2017:1–13. https://doi.org/10.1155/2017/8416763

    Article  CAS  Google Scholar 

  134. Cerf ME (2013) Beta cell dysfunction and insulin resistance. Front Endocrinol 4:e00037. https://doi.org/10.3389/fendo.2013.00037

    Article  Google Scholar 

  135. Keane KN, Cruzat VF, Carlessi R, de Bittencourt PIH, Newsholme P (2015) Molecular events linking oxidative stress and inflammation to insulin resistance and β-cell dysfunction. Oxid Med Cell Longev 2015:1–15. https://doi.org/10.1155/2015/181643

    Article  Google Scholar 

  136. Spiro A, Buttriss JL (2014) Vitamin D: an overview of vitamin D status and intake in Europe. Nutr Bull 39(4):322–350. https://doi.org/10.1111/nbu.12108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Tangvarasittichai S (2015) Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 6(3):456. https://doi.org/10.4239/wjd.v6.i3.456

    Article  PubMed  PubMed Central  Google Scholar 

  138. Gradinaru D, Borsa C, Ionescu C, Margina D, Prada GI, Jansen E (2012) Vitamin D status and oxidative stress markers in the elderly with impaired fasting glucose and type 2 diabetes mellitus. Aging Clin Exp Res 24(6):595–602. https://doi.org/10.3275/8591

    Article  CAS  PubMed  Google Scholar 

  139. Beaupere C, Liboz A, Fève B, Blondeau B, Guillemain G (2021) Molecular mechanisms of glucocorticoid-induced insulin resistance. Int J Mol Sci 22(2):1–30. https://doi.org/10.3390/ijms22020623

    Article  CAS  Google Scholar 

  140. Wang J, Li H (2020) Erratum: treatment of glucocorticoid-induced osteoporosis with bisphosphonates alone, vitamin D alone or a combination treatment in eastern asians: a meta-analysis. Curr Pharm Des 26(22):2682–2682. https://doi.org/10.2174/138161282622200624180506

    Article  Google Scholar 

  141. Mauvais-Jarvis F, Manson JAE, Stevenson JC, Fonseca VA (2017) Menopausal hormone therapy and type 2 diabetes prevention: evidence, mechanisms, and clinical implications. Endocr Rev 38(3):173–188. https://doi.org/10.1210/er.2016-1146

    Article  PubMed  PubMed Central  Google Scholar 

  142. Kinuta K, Tanaka H, Moriwake T, Aya K, Kato S, Seino Y (2000) Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology 141(4):1317–1324. https://doi.org/10.1210/endo.141.4.7403

    Article  CAS  PubMed  Google Scholar 

  143. Fondjo LA, Sakyi SA, Owiredu WKBA et al (2018) Evaluating vitamin D status in pre- and postmenopausal type 2 diabetics and its association with glucose homeostasis. Biomed Res Int 2018:1–12. https://doi.org/10.1155/2018/9369282

    Article  CAS  Google Scholar 

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Acknowledgements

Author of this manuscript thankful to The People’s Hospital of Beilun District, China for providing necessary support for presented manuscript.

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  1. Department of Stomatology, The People’s Hospital of Beilun District, Ningbo, 315800, China

    Cheng Dong & Xuzhi Hu

  2. Department of Pharmacology, Amity Institute of Pharmacy, Amity University, Noida, U.P., India

    Alok Shiomurti Tripathi

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CD and XH generated the idea, searched the literature and interpreted the data and drafted the rough version of manuscript. AST wrote and critically revised the paper. All authors read and approved the final manuscript.

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Dong, C., Hu, X. & Tripathi, A.S. A brief review of vitamin D as a potential target for the regulation of blood glucose and inflammation in diabetes-associated periodontitis. Mol Cell Biochem 477, 2257–2268 (2022). https://doi.org/10.1007/s11010-022-04445-w

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