Sirtuin 1 ve Sirtuin 2’nin Tip 2 Diyabet ile İlişkisi

Year 2021, Volume: 5 Issue: 1, 81 - 88, 24.04.2021

İlke Ulu , Güneş Çakmak Genç , Sevim Karakaş Çelik

https://doi.org/10.25048/tudod.808316

Cited By: 3

Abstract

Diabetes mellitus, bütün dünyada ve bütün yaş gruplarında en sık görülen endokrin hastalıktır. Tip 2 diabet; diabet vakalarının yaklaşık %80-90’nı oluşturan ve tipik olarak ileri yaşlarda ortaya çıkan bir hastalıktır. Tip 2 diabet patogenezi oldukça karmaşıktır ve birçok yönden halen tartışma konusudur. Kalıtım poligeniktir ve çevresel faktörlerle güçlü bir ilişkisi mevcuttur. Bozulmuş insulin sekresyonu ve bozulmuş insulin sensitivitesi söz konusudur. Sirtuin ailesi (SIRT) NAD+ bağımlı deasetilazlar olup memelilerde, maya ve yüksek organizmalarda histon deasitalasyonu ve DNA stabilizasyonunu sağlar. Yapılan çalışmalarda onkogenez, uzun ömür, metabolik regülasyon ve nörodejeneratif hastalıklar ile ilişkili olduğu gösterilmiştir. Hücre döngüsünün düzenlenmesi, apoptoz, mitokondriyal biyogenez, lipid metabolizması, yağ asidi oksidasyonu, hücresel stres yanıtı, insülin salgılanması, yaşlanma ve inflamasyon gibi pek çok fizyolojik süreçte rol oynayan sirtuinlerin son yıllarda diyabet patogenezinde de oldukça önemli rolü olduğu tespit edilmiştir.

Keywords

Sirtuin, SIRT1, SIRT2, Tip 2 Diabet

Relationship Between Sirtuin 1 and Sirtuin 2 with Type 2 Diabetes

Abstract

Diabetes mellitus is the most common endocrine disease in the world and in all age groups. Type 2 diabetes is a disease that constitutes approximately 80-90% of diabetes cases and typically occurs in advanced ages. The pathogenesis of type 2 diabetes is quite complex and is still a matter of debate in many aspects. Heredity is polygenic and has a strong relationship with environmental factors. There is impaired insulin secretion and impaired insulin sensitivity. The Sirtuin family (SIRT) members are NAD+ dependent deacetylases that provide histone deacetylation and DNA stabilization in mammals, yeast and higher organisms. Studies have shown that it is associated with oncogenesis, longevity, metabolic regulation and neurodegenerative diseases. Sirtuins, which play a role in many physiological processes such as cell cycle regulation, apoptosis, mitochondrial biogenesis, lipid metabolism, fatty acid oxidation, cellular stress response, insulin
secretion, aging, and inflammation, have been found to have a significant role in diabetes pathogenesis in recent years.

Keywords

Sirtuin, SIRT1, SIRT2, Type 2 Diabetes mellitus

References

• 1. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature. 2001;414(6865):799- 806.
• 2. Satman I, Omer B, Tutuncu Y, Kalaca S, Gedik S, Dinccag N ve ark. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013;(28):169-180.
• 3. Whiting DR, Guariguata L, Weil C, Shaw J. IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94(3): 311-321.
• 4. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;(138):271-281.
• 5. International Diabetes Federation. IDF Diabetes Atlas, 8th edn. Brussels, Belgium: International Diabetes Federation, 2017. http://www.diabetesatlas.org. Eriºim Tarihi: 10 Nisan 2018.
• 6. American Diabetes Association. 1. Improving care and promoting health in populations: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019;42(1):7-12.
• 7. Gan SK, Kriketos AD, Ellis BA, Thompson CH, Kraegen EW, Chisholm DJ. Changes in aerobic capacity and visceral fat but not myocyte lipid levels predict increased insulin action after exercise in overweight and obese men. Diabetes Care. 2003;26(6):1706-1713.
• 8. Williams KV, Kelley DE. Metabolic consequences of weight loss on glucose metabolism and insulin action in type 2 diabetes. Diabetes Obes Metab. 2000;(2):121-129.
• 9. Poulose N, Raju R. Sirtuin regulation in aging and injury. Biochim Biophys Acta. 2015;1852(11):2442-2455.
• 10. Michan S, Sinclair D. Sirtuins in mammals: Insights into their biological function. Biochem J. 2007;404(1):1-13.
• 11. Flick F, Lüscher B. Regulation of sirtuin function by posttranslational modifications. Front Pharmacol. 2012;3:29. 12. Roth M, Chen WY. Sorting out functions of sirtuins in cancer. Oncogene. 2014;33(13):1609-1620.
• 13. Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014;25(3):138-145.
• 14. Taddei A, Roche D, Bickmore WA, Almouzni G. The effects of histone deacetylase inhibitors on heterochromatin: Implications for anticancer therapy? EMBO Rep. 2005;6(6):520-524.
• 15. Palmirotta R, Cives M, Della-Morte D, et al. Sirtuins and cancer: Role in the epithelial-mesenchymal transition. Oxid Med Cell Longev. 2016;2016:3031459.
• 16. Roth M, Chen WY. Sorting out functions of sirtuins in cancer. Oncogene. 2014; 33(13): 1609-1620.
• 17. Vaquero A, Scher M, Lee D, Erdjument-Bromage H, Tempst P, Reinberg D. Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. Mol Cell. 2004;16(1): 93-105.
• 18. Kitada M, Koya D. SIRT1 in type 2 diabetes: Mechanisms and therapeutic potential. Diabetes Metab J. 2013;37(5):315-325.
• 19. Liu T, Liu PY, Marshall GM. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 2009;69(5): 1702-1705.
• 20. Bordone L, Guarente L. Calorie restriction, SIRT1 and metabolism: Understanding longevity. Nat Rev Mol Cell Biol. 2005;6:298-305.
• 21. Bordone L, Motta M C, Picard F, Robinson A, Jhala US, Apfeld J, McDonagh T, Lemieux M, McBurney M, Szilvasi A, Easlon EJ, Lin SJ, Guarente L. Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. PLoS Biol. 2006;4(2): e31.
• 22. Lee JH, Song MY, Song EK, Kim EK, Moon WS, Han MK, Park JW, Kwon KB, Park BH. Overexpression of SIRT1 protects pancreatic beta-cells against cytokine toxicity by suppressing the nuclear factor-kappaB signaling pathway. Diabetes. 2009;58:344-351.
• 23. Moynihan KA, Grimm AA, Plueger MM, Bernal-Mizrachi E, Ford E, Cras-Meneur C, Permutt MA, Imai S. Increased dosage of mammalian Sir2 in pancreatic beta cells enhances glucose-stimulated insulin secretion in mice. Cell Metab 2005;2:105-117.
• 24. Ramsey KM, Mills KF, Satoh A, Imai S. Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell. 2008;7:78-88.
• 25. Frojdo S, Durand C, Molin L, Carey AL, El-Osta A, Kingwell BA, Febbraio MA, Solari F, Vidal H, Pirola L. Phosphoinositide 3-kinase as a novel functional target for the regulation of the insulin signaling pathway by SIRT1. Mol Cell Endocrinol. 2011;335:166-176.
• 26. Zhang J. The direct involvement of SirT1 in insulin-induced insulin receptor substrate-2 tyrosine phosphorylation. J Biol Chem. 2007;282:34356-34364.
• 27. Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008; 582(1):46-53.
• 28. Puigserver P, Spiegelman BM. Peroxisome proliferatoractivated receptor-gamma coactivator 1 alpha (PGC-1 alpha): Transcriptional coactivator and metabolic regulator. Endocr Rev. 2003; 24(1):78-90.
• 29. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005; 434(7029):113-118.
• 30. Kitada M, Koya D. SIRT1 in Type 2 diabetes: Mechanisms and therapeutic potential. Diabetes Metab J. 2013;37(5):315-325.
• 31. Rodgers JT, Puigserver P. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci U S A. 2007; 104(31):12861-12866.
• 32. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab. 2009; 9(4):327-338.
• 33. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995; 83(6):841-850.
• 34. Ponugoti B, Kim DH, Xiao Z, Smith Z, Miao J, Zang M, Wu SY, Chiang CM, Veenstra TD, Kemper JK. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem. 2010;285(44):33959-339570.
• 35. Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L. Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature. 2004;429:771-776.
• 36. Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, Rosenbaum M, Zhao Y, Gu W, Farmer SR, Accili D. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Cell. 2012;150:620-632.
• 37. Smith JS, Brachmann CB, Celic I, Kenna MA, Muhammad S, Starai VJ, Avalos JL, Escalante-Semerena JC, Grubmeyer C, Wolberger C, Boeke JD. A phylogenetically conserved NADdependent protein deacetylase activity in the Sir2 protein family. Proc Natl Acad Sci USA. 2000;97:6658-6663.
• 38. De Oliveira RM, Sarkander J, Kazantsev AG, Outeiro TF. SIRT2 as a therapeutic target for age-related disorders. Front Pharmacol, 2012; 3: 82.
• 39. North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003; 11(2): 437-444.
• 40. Rothgiesser KM, Erener S, Waibel S, Lüscher B, Hottiger MO. SIRT2 regulates NF-κB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci. 2010; 123(Pt 24): 4251- 4258.
• 41. Vaquero A, Scher MB, Lee DH, Sutton A, Cheng HL, Alt FW, Serrano L, Sternglanz R, Reinberg D. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev. 2006; 20(10): 1256-1261.
• 42. Gomes P, Fleming Outeiro T, Cavadas C. Emerging role of Sirtuin 2 in the regulation of mammalian metabolism. Trends Pharmacol Sc. 2015;36:756-768.
• 43. Jing E, Gesta S, Kahn CR. SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. Cell Metab. 2007; 6(2): 105-114.
• 44. Wang F, Tong Q. SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1’s repressive interaction with PPARgamma. Mol Biol Cell.2009;20:801-808.
• 45. Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011; 43(1): 33-44.
• 46. Zhang M, Pan Y, Dorfman RG, Yin Y, Zhou Q, Huang S, Liu J, Zhao S. Sirtinol promotes PEPCK1 degradation and inhibits gluconeogenesis by inhibiting deacetylase SIRT2. Sci Rep. 2017;7(1):7.
• 47. Watanabe H, Inaba Y, Kimura K, Matsumoto M, Kaneko S, Kasuga M, Inoue H. Sirt2 facilitates hepatic glucose uptake by deacetylating glucokinase regulatory protein. Nat Commun. 2018; 9(1):30.
• 48. Han J, Wei M, Wang Q, Li X, Zhu C, Mao Y, Wei L, Sun Y, Jia W. Association of genetic variants of SIRT1 with type 2 diabetes mellitus. Gene Expr. 2015;16(4):177-185.
• 49. Gambino R, Fanni G, Togliatto G, Ponzo V, Goitre I, Cassader M, Brizzi MF, Bo S. Rs12778366 single nucleotide polymorphism of Sirtuin 1 (SIRT1) and response to resveratrol supplementation in patients with type 2 diabetes mellitus. Acta Diabetol. 2019;56(8):963-966.
• 50. Peng Y, Zhang G, Tang H, Dong L, Gao C, Yang X, Peng Y, Xu Y. Influence of SIRT1 polymorphisms for diabetic foot susceptibility and severity. Medicine (Baltimore). 2018;97(28):e11455.
• 51. Zhuanping Z, Rifang L, Qing C, Sidong C. The Association between SIRT1 genetic variation and type 2 diabetes mellitus is influenced by dietary intake in elderly Chinese. Iran J Public Health. 2018;47(9):1272-1280.
• 52. Zhao Y, Wei J, Hou X, Liu H, Guo F, Zhou Y, Zhang Y, Qu Y, Gu J, Zhou Y, Jia X, Qin G, Feng L. SIRT1 rs10823108 and FOXO1 rs17446614 responsible for genetic susceptibility to diabetic nephropathy. Sci Rep. 2017;7(1):10285.
• 53. Domínguez-Cruz MG, Muñoz ML, Totomoch-Serra A, García-Escalante MG, Burgueño J, Valadez-González N, Pinto-Escalante D, Díaz-Badillo A. Maya gene variants related to the risk of type 2 diabetes in a family-based association study. Gene. 2020;730:144259.
• 54. Maeda S, Koya D, Araki SI, Babazono T, Umezono T, Toyoda M, Kawai K, Imanishi M, Uzu T, Suzuki D, Maegawa H, Kashiwagi A, Iwamoto Y, Nakamura Y. Association between single nucleotide polymorphisms within genes encoding sirtuin families and diabetic nephropathy in Japanese subjects with type 2 diabetes. Clin Exp Nephrol. 2011;15(3):381-390.
• 55. Rai E, Sharma S, Kaul S, Jain K, Matharoo K, Bhanwer AS, Bamezai RN. The interactive effect of SIRT1 promoter region polymorphism on type 2 diabetes susceptibility in the North Indian population. PLoS One. 2012;7(11):e48621.
• 56. Dong Y, Guo T, Traurig M, Mason CC, Kobes S, Perez J, Knowler WC, Bogardus C, Hanson RL, Baier LJ. SIRT1 is associated with a decrease in acute insulin secretion and a sex specific increase in risk for type 2 diabetes in Pima Indians. Mol Genet Metab. 2011;104(4):661-665.
• 57. Liu T, Yang W, Pang S, Yu S, Yan B. Functional genetic variants within the SIRT2 gene promoter in type 2 diabetes mellitus. Diabetes Res Clin Pract. 2018;137:200-207.
• 58. Zhou S, Tang X, Chen HZ. Sirtuins and Insulin Resistance. Front Endocrinol (Lausanne). 2018;9:748.