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Role of melatonin in metabolic regulation

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Abstract

Although the human genome has remained unchanged over the last 10,000 years, our lifestyle has become progressively more divergent from those of our ancient ancestors. This maladaptive change became apparent with the Industrial Revolution and has been accelerating in recent decades. Socially, we are people of the 21st century, but genetically we remain similar to our early ancestors. In conjunction with this discordance between our ancient, genetically-determined biology and the nutritional, cultural and activity patterns in contemporary Western populations, many diseases have emerged. Only a century ago infectious disease was a major cause of mortality, whereas today non-infectious chronic diseases are the greatest cause of death in the world. Epidemics of metabolic diseases (e.g., cardiovascular diseases, type 2 diabetes, obesity, metabolic syndrome and certain cancers) have become major contributors to the burden of poor health and they are presently emerging or accelerating, in most developing countries. One major lifestyle consequence is light at night and subsequent disrupted circadian rhythms commonly referred to as circadian disruption or chronodisruption. Mounting evidence reveals that particularly melatonin rhythmicity has crucial roles in a variety of metabolic functions as an anti-oxidant, anti-inflammatory chronobiotic and possibly as an epigenetic regulator. This paper provides a brief outline about metabolic dysregulation in conjunction with a disrupted melatonin rhythm.

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References

  1. Meigs JB. Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol. 2000;152:908–11. discussion 912.

    CAS  PubMed  Google Scholar 

  2. Leiter LA, Ceriello A, Davidson JA, Hanefeld M, Monnier L, Owens DR, et al. Postprandial glucose regulation: new data and new implications. Clin Ther. 2005;27(Suppl B):S42–56.

    CAS  PubMed  Google Scholar 

  3. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004;24:816–23.

    CAS  PubMed  Google Scholar 

  4. Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care. 1999;22:920–4.

    CAS  PubMed  Google Scholar 

  5. Bonora E, Corrao G, Bagnardi V, Ceriello A, Comaschi M, Montanari P, et al. Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia. 2006;49:846–54.

    CAS  PubMed  Google Scholar 

  6. Liu BF, Miyata S, Hirota Y, Higo S, Miyazaki H, Fukunaga M, et al. Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells. Kidney Int. 2003;63:947–57.

    CAS  PubMed  Google Scholar 

  7. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26:881–5.

    PubMed  Google Scholar 

  8. El-Kebbi IM, Ziemer DC, Cook CB, Gallina DL, Barnes CS, Phillips LS. Utility of casual postprandial glucose levels in type 2 diabetes management. Diabetes Care. 2004;27:335–9.

    PubMed  Google Scholar 

  9. Halimi S, Raskin P, Liebl A, Kawamori R, Fulcher G, Yan G. Efficacy of biphasic insulin aspart in patients with type 2 diabetes. Clin Ther. 2005;27(Suppl B):S57–74.

    CAS  PubMed  Google Scholar 

  10. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854–865.

  11. Cavalot F, Petrelli A, Traversa M, Bonomo K, Fiora E, Conti M, et al. Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab. 2006;91:813–9.

    CAS  PubMed  Google Scholar 

  12. O’Keefe JH, Bell DS. Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol. 2007;100:899–904.

    PubMed  Google Scholar 

  13. Sasso FC, Carbonara O, Nasti R, Campana B, Marfella R, Torella M, et al. Glucose metabolism and coronary heart disease in patients with normal glucose tolerance. Jama. 2004;291:1857–63.

    CAS  PubMed  Google Scholar 

  14. Anderson RA, Evans ML, Ellis GR, Graham J, Morris K, Jackson SK, et al. The relationships between post-prandial lipaemia, endothelial function and oxidative stress in healthy individuals and patients with type 2 diabetes. Atherosclerosis. 2001;154:475–83.

    CAS  PubMed  Google Scholar 

  15. Gaziano JM, Hennekens CH, O’Donnell CJ, Breslow JL, Buring JE. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96:2520–5.

    CAS  PubMed  Google Scholar 

  16. Teno S, Uto Y, Nagashima H, Endoh Y, Iwamoto Y, Omori Y, et al. Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. Diabetes Care. 2000;23:1401–6.

    CAS  PubMed  Google Scholar 

  17. Balsalobre A. Clock genes in mammalian peripheral tissues. Cell Tissue Res. 2002;309:193–9.

    CAS  PubMed  Google Scholar 

  18. Navara KJ, Nelson RJ. The dark side of light at night: physiological, epidemiological, and ecological consequences. J Pineal Res. 2007;43:215–24.

    CAS  PubMed  Google Scholar 

  19. Erren TC, Reiter RJ. Defining chronodisruption. J Pineal Res. 2009;46:245–7.

    CAS  PubMed  Google Scholar 

  20. Kreier F, Yilmaz A, Kalsbeek A, Romijn JA, Sauerwein HP, Fliers E, et al. Hypothesis: shifting the equilibrium from activity to food leads to autonomic unbalance and the metabolic syndrome. Diabetes. 2003;52:2652–6.

    CAS  PubMed  Google Scholar 

  21. Hamilton MT, Hamilton DG, Zderic TW. Role of low energy expenditure and sitting in obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Diabetes. 2007;56:2655–67.

    CAS  PubMed  Google Scholar 

  22. Fung TT, Hu FB, Yu J, Chu NF, Spiegelman D, Tofler GH, et al. Leisure-time physical activity, television watching, and plasma biomarkers of obesity and cardiovascular disease risk. Am J Epidemiol. 2000;152:1171–8.

    CAS  PubMed  Google Scholar 

  23. Gao X, Nelson ME, Tucker KL. Television viewing is associated with prevalence of metabolic syndrome in Hispanic elders. Diabetes Care. 2007;30:694–700.

    PubMed  Google Scholar 

  24. Salti R, Tarquini R, Stagi S, Perfetto F, Cornelissen G, Laffi G, et al. Age-dependent association of exposure to television screen with children’s urinary melatonin excretion? Neuro Endocrinol Lett. 2006;27:73–80.

    CAS  PubMed  Google Scholar 

  25. la Fleur SE, Kalsbeek A, Wortel J, Fekkes ML, Buijs RM. A daily rhythm in glucose tolerance: a role for the suprachiasmatic nucleus. Diabetes. 2001;50:1237–43.

    PubMed  Google Scholar 

  26. Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hyperten. 2009;27(Suppl 6):S17–20.

    Google Scholar 

  27. la Fleur SE, Kalsbeek A, Wortel J, van der Vliet J, Buijs RM. Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations. J Neuroendocrinol. 2001;13:1025–32.

    PubMed  Google Scholar 

  28. Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, Muhlbauer E. Melatonin and type 2 diabetes—a possible link? J Pineal Res. 2007;42:350–8.

    CAS  PubMed  Google Scholar 

  29. Peschke E, Frese T, Chankiewitz E, Peschke D, Preiss U, Schneyer U, et al. Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status. J Pineal Res. 2006;40:135–43.

    CAS  PubMed  Google Scholar 

  30. Goncharova ND, Vengerin AA, Khavinson V, Lapin BA. Pineal peptides restore the age-related disturbances in hormonal functions of the pineal gland and the pancreas. Exp Gerontol. 2005;40:51–7.

    CAS  PubMed  Google Scholar 

  31. Ha E, Yim SV, Chung JH, Yoon KS, Kang I, Cho YH, et al. Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells. J Pineal Res. 2006;41:67–72.

    CAS  PubMed  Google Scholar 

  32. Sudnikovich EJ, Maksimchik YZ, Zabrodskaya SV, Kubyshin VL, Lapshina EA, Bryszewska M, et al. Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats. Eur J Pharmacol. 2007;569:180–7.

    CAS  PubMed  Google Scholar 

  33. Tutuncu NB, Batur MK, Yildirir A, Tutuncu T, Deger A, Koray Z, et al. Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy. J Pineal Res. 2005;39:43–9.

    CAS  PubMed  Google Scholar 

  34. Kireev RA, Tresguerres ACF, Garcia C, Ariznavarreta C, Vara E, Tresguerres JAF. Melatonin is able to prevent the liver of old castrated female rats from oxidative and pro-inflammatory damage. J Pineal Res. 2008;45:394–402.

    CAS  PubMed  Google Scholar 

  35. Peyrot F, Ducrocq C. Potential role of tryptophan derivatives in stress responses characterized by the generation of reactive oxygen and reactive nitrogen species. J Pineal Res. 2008;45:235–46.

    CAS  PubMed  Google Scholar 

  36. Tengattini S, Reiter RJ, Tan DX, Terran MP, Rodella LF, Rezzani R. Cardiovascular diseases: protective effects of melatonin. J. Pineal Res. 2008;44:16–25.

    CAS  PubMed  Google Scholar 

  37. Reiter RJ, Tan DX, Jou MJ, Korkmaz A, Manchester LC, Paredes SD. Biogenic amines in the reduction of oxidative stress: melatonin and its metabolites. Neuro Endocrinol Lett. 2008;29:391–8.

    PubMed  Google Scholar 

  38. Hussain SA, Khadim HM, Khalaf BH, Ismail SH, Hussein KI, Sahib AS. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med J. 2006;27:1483–8.

    PubMed  Google Scholar 

  39. Kadhim HM, Ismail SH, Hussein KI, Bakir IH, Sahib AS, Khalaf BH, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res. 2006;41:189–93.

    CAS  PubMed  Google Scholar 

  40. Peschke E. Melatonin, endocrine pancreas and diabetes. J Pineal Res. 2008;44:26–40.

    CAS  PubMed  Google Scholar 

  41. Millar-Craig MW, Bishop CN, Raftery EB. Circadian variation of blood-pressure. Lancet. 1978;1:795–7.

    CAS  PubMed  Google Scholar 

  42. Anan F, Takahashi N, Ooie T, Yufu K, Saikawa T, Yoshimatsu H. Role of insulin resistance in nondipper essential hypertensive patients. Hypertens Res. 2003;26:669–76.

    CAS  PubMed  Google Scholar 

  43. Kotsis V, Stabouli S, Bouldin M, Low A, Toumanidis S, Zakopoulos N. Impact of obesity on 24-hour ambulatory blood pressure and hypertension. Hypertension. 2005;45:602–7.

    CAS  PubMed  Google Scholar 

  44. Pierdomenico SD, Bucci A, Costantini F, Lapenna D, Cuccurullo F, Mezzetti A. Circadian blood pressure changes and myocardial ischemia in hypertensive patients with coronary artery disease. J Am Coll Cardiol. 1998;31:1627–34.

    CAS  PubMed  Google Scholar 

  45. Palatini P. Non-dipping in hypertension: still a challenging problem. J Hypertens. 2004;22:2269–72.

    CAS  PubMed  Google Scholar 

  46. Leitschuh M, Cupples LA, Kannel W, Gagnon D, Chobanian A. High-normal blood pressure progression to hypertension in the Framingham Heart Study. Hypertension. 1991;17:22–7.

    CAS  PubMed  Google Scholar 

  47. Kawashima K, Nagakura A, Wurzburger RJ, Spector S. Melatonin in serum and the pineal of spontaneously hypertensive rats. Clin Exp Hypertens A. 1984;6:1517–28.

    CAS  PubMed  Google Scholar 

  48. Kawashima K, Miwa Y, Fujimoto K, Oohata H, Nishino H, Koike H. Antihypertensive action of melatonin in the spontaneously hypertensive rat. Clin Exp Hypertens A. 1987;9:1121–31.

    CAS  PubMed  Google Scholar 

  49. Holmes SW, Sugden D. The effect of melatonin on pinealectomy-induced hypertension in the rat. Br J Pharmacol. 1976;56:360P–1.

    CAS  PubMed  Google Scholar 

  50. Nava M, Quiroz Y, Vaziri N, Rodriguez-Iturbe B. Melatonin reduces renal interstitial inflammation and improves hypertension in spontaneously hypertensive rats. Am J Physiol Renal Physiol. 2003;284:F447–54.

    CAS  PubMed  Google Scholar 

  51. Girouard H, Chulak C, LeJossec M, Lamontagne D, de Champlain J. Chronic antioxidant treatment improves sympathetic functions and beta-adrenergic pathway in the spontaneously hypertensive rats. J Hypertens. 2003;21:179–88.

    CAS  PubMed  Google Scholar 

  52. Girouard H, de Champlain J. Inhibitory effect of melatonin on alpha1-adrenergic-induced vasoconstriction in mesenteric beds of spontaneously hypertensive rats. Am J Hypertens. 2004;17:339–46.

    CAS  PubMed  Google Scholar 

  53. Girouard H, Denault C, Chulak C, de Champlain J. Treatment by n-acetylcysteine and melatonin increases cardiac baroreflex and improves antioxidant reserve. Am J Hypertens. 2004;17:947–54.

    CAS  PubMed  Google Scholar 

  54. Deniz E, Sahna E, Aksulu HE. Nitric oxide synthase inhibition in rats: melatonin reduces blood pressure and ischemia/reperfusion-induced infarct size. Scand Cardiovasc J. 2006;40:248–52.

    CAS  PubMed  Google Scholar 

  55. Jonas M, Garfinkel D, Zisapel N, Laudon M, Grossman E. Impaired nocturnal melatonin secretion in non-dipper hypertensive patients. Blood Press. 2003;12:19–24.

    PubMed  Google Scholar 

  56. Cagnacci A, Cannoletta M, Renzi A, Baldassari F, Arangino S, Volpe A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18:1614–8.

    CAS  PubMed  Google Scholar 

  57. Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension. 2004;43:192–7.

    CAS  PubMed  Google Scholar 

  58. Cavallo A, Daniels SR, Dolan LM, Bean JA, Khoury JC. Blood pressure-lowering effect of melatonin in type 1 diabetes. J Pineal Res. 2004;36:262–6.

    CAS  PubMed  Google Scholar 

  59. Simko F, Paulis L. Melatonin as a potential antihypertensive treatment. J Pineal Res. 2007;42:319–22.

    CAS  PubMed  Google Scholar 

  60. Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology. 1999;140:1009–12.

    CAS  PubMed  Google Scholar 

  61. Prunet-Marcassus B, Desbazeille M, Bros A, Louche K, Delagrange P, Renard P, et al. Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity. Endocrinology. 2003;144:5347–52.

    CAS  PubMed  Google Scholar 

  62. Wolden-Hanson T, Mitton DR, McCants RL, Yellon SM, Wilkinson CW, Matsumoto AM, et al. Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology. 2000;141:487–97.

    CAS  PubMed  Google Scholar 

  63. Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, et al. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 2002;109:307–20.

    CAS  PubMed  Google Scholar 

  64. Rudic RD, McNamara P, Curtis AM, Boston RC, Panda S, Hogenesch JB, et al. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2004;2:e377.

    PubMed  Google Scholar 

  65. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, et al. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 2005;308:1043–5.

    CAS  PubMed  Google Scholar 

  66. Shimba S, Ishii N, Ohta Y, Ohno T, Watabe Y, Hayashi M, et al. Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci U S A. 2005;102:12071–6.

    CAS  PubMed  Google Scholar 

  67. Alonso-Vale MI, Andreotti S, Mukai PY, Borges-Silva CD, Peres SB, Cipolla-Neto J, et al. Melatonin and the circadian entrainment of metabolic and hormonal activities in primary isolated adipocytes. J Pineal Res. 2008;45:422–9.

    CAS  PubMed  Google Scholar 

  68. Lima FB, Machado UF, Bartol I, Seraphim PM, Sumida DH, Moraes SM, et al. Pinealectomy causes glucose intolerance and decreases adipose cell responsiveness to insulin in rats. Am J Physiol. 1998;275:E934–41.

    CAS  PubMed  Google Scholar 

  69. Picinato MC, Haber EP, Carpinelli AR, Cipolla-Neto J. Daily rhythm of glucose-induced insulin secretion by isolated islets from intact and pinealectomized rat. J Pineal Res. 2002;33:172–7.

    CAS  PubMed  Google Scholar 

  70. Alonso-Vale MI, Andreotti S, Peres SB, Anhe GF, das Neves Borges-Silva C, Neto JC, et al. Melatonin enhances leptin expression by rat adipocytes in the presence of insulin. Am J Physiol Endocrinol Metab. 2005;288:E805–12.

    CAS  PubMed  Google Scholar 

  71. Alonso-Vale MI, Andreotti S, Borges-Silva CN, Mukai PY, Cipolla-Neto J, Lima FB. Intermittent and rhythmic exposure to melatonin in primary cultured adipocytes enhances the insulin and dexamethasone effects on leptin expression. J Pineal Res. 2006;41:28–34.

    CAS  PubMed  Google Scholar 

  72. Stefulj J, Hortner M, Ghosh M, Schauenstein K, Rinner I, Wolfler A, et al. Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat. J Pineal Res. 2001;30:243–7.

    CAS  PubMed  Google Scholar 

  73. Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci. 2002;47:2336–48.

    CAS  PubMed  Google Scholar 

  74. Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ. One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res. 2007;42:28–42.

    CAS  PubMed  Google Scholar 

  75. Reiter RJ, Paredes SD, Korkmaz A, Jou MJ, Tan DX. Melatonin combats molecular terrorism at the mitochondrial level. Interdisc Toxicol. 2008;1:137–49.

    Google Scholar 

  76. Ho E, Pellegrino S, Gitto P, Barberi I, Reiter RJ. Oxidative stress in the newborn in the pre- and post-natal period and the clinical utility of melatonin. J Pineal Res. 2009;46:128–39.

    Google Scholar 

  77. Jaworek J, Nawrot-Porabka K, Leja-Szpak A, Bonior J, Szklarczyk J, Kot M, et al. Melatonin as modulator of pancreatic enzyme secretion and pancreatoprotector. J Physiol Pharmacol. 2007;58(Suppl 6):65–80.

    PubMed  Google Scholar 

  78. Fischer TW, Slominski A, Zmijewski MA, Reiter RJ, Paus R. Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair. Exp Dermatol. 2008;17:713–30.

    CAS  PubMed  Google Scholar 

  79. Fischer TW, Slominski A, Tobin DJ, Paus R. Melatonin and the hair follicle. J Pineal Res. 2008;44:1–15.

    CAS  PubMed  Google Scholar 

  80. Korkmaz A, Topal T, Oter S, Tan DX, Reiter RJ. Hyperglycemia-related pathophysiologic mechanisms and potential beneficial actions of melatonin. Mini Rev Med Chem. 2008;8:1144–53.

    CAS  PubMed  Google Scholar 

  81. Gilad E, Cuzzocrea S, Zingarelli B, Salzman AL, Szabo C. Melatonin is a scavenger of peroxynitrite. Life Sci. 1997;60:PL169–74.

    CAS  PubMed  Google Scholar 

  82. Ucar M, Korkmaz A, Reiter RJ, Yaren H, Oter S, Kurt B, et al. Melatonin alleviates lung damage induced by the chemical warfare agent nitrogen mustard. Toxicol Lett. 2007;173:124–31.

    CAS  PubMed  Google Scholar 

  83. Topal T, Oztas Y, Korkmaz A, Sadir S, Oter S, Coskun O, et al. Melatonin ameliorates bladder damage induced by cyclophosphamide in rats. J Pineal Res. 2005;38:272–7.

    CAS  PubMed  Google Scholar 

  84. Higashi Y, Nakagawa K, Kimura M, Noma K, Hara K, Sasaki S, et al. Circadian variation of blood pressure and endothelial function in patients with essential hypertension: a comparison of dippers and non-dippers. J Am Coll Cardiol. 2002;40:2039–43.

    PubMed  Google Scholar 

  85. Mei Q, Yu JP, Xu JM, Wei W, Xiang L, Yue L. Melatonin reduces colon immunological injury in rats by regulating activity of macrophages. Acta Pharmacol Sin. 2002;23:882–6.

    CAS  PubMed  Google Scholar 

  86. Wang H, Wei W, Shen YX, Dong C, Zhang LL, Wang NP, et al. Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide. World J Gastroenterol. 2004;10:2690–6.

    CAS  PubMed  Google Scholar 

  87. Gocgeldi E, Uysal B, Korkmaz A, Ogur R, Reiter RJ, Kurt B, et al. Establishing the use of melatonin as an adjuvant therapeutic against paraquat-induced lung toxicity in rats. Exp Biol Med (Maywood). 2008;233:1133–41.

    CAS  Google Scholar 

  88. Cuzzocrea S, Reiter RJ. Pharmacological actions of melatonin in acute and chronic inflammation. Curr Top Med Chem. 2002;2:153–65.

    CAS  PubMed  Google Scholar 

  89. Pacher P, Szabo C. Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal. 2005;7:1568–80.

    CAS  PubMed  Google Scholar 

  90. Rodriguez MI, Carretero M, Escames G, Lopez LC, Maldonado MD, Tan DX, et al. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Radic Res. 2007;41:15–24.

    CAS  PubMed  Google Scholar 

  91. Reiter RJ, Tan DX, Pappolla MA. Melatonin relieves the neural oxidative burden that contributes to dementias. Ann N Y Acad Sci. 2004;1035:179–96.

    CAS  PubMed  Google Scholar 

  92. Reiter RJ, Tan DX, Manchester LC, Terron MP, Flores LJ, Koppisetti S. Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv Med Sci. 2007;52:11–28.

    CAS  PubMed  Google Scholar 

  93. Suzuki N, Somei M, Seki A, Reiter RJ, Hattori A. Novel bromomelatonin derivatives as potentially effective drugs to treat bone diseases. J Pineal Res. 2008;45:229–34.

    CAS  PubMed  Google Scholar 

  94. Smirnov AN. Nuclear melatonin receptors. Biochemistry (Mosc). 2001;66:19–26.

    CAS  Google Scholar 

  95. Tang WY, Ho SM. Epigenetic reprogramming and imprinting in origins of disease. Rev Endocr Metab Disord. 2007;8:173–82.

    PubMed  Google Scholar 

  96. Miremadi A, Oestergaard MZ, Pharoah PD, Caldas C. Cancer genetics of epigenetic genes. Hum Mol Genet. 2007;16(Spec No 1):R28–49.

    CAS  PubMed  Google Scholar 

  97. Sharma R, Ottenhof T, Rzeczkowska PA, Niles LP. Epigenetic targets for melatonin: induction of histone H3 hyperacetylation and gene expression in C17.2 neural stem cells. J Pineal Res. 2008;45:277–84.

    CAS  PubMed  Google Scholar 

  98. Korkmaz A, Reiter RJ. Epigenetic regulation: a new research area for melatonin? J Pineal Res. 2008;44:41–4.

    CAS  PubMed  Google Scholar 

  99. Korkmaz A, Sanchez-Barcelo EJ, Tan DX, Reiter RJ. Role of melatonin in the epigenetic regulation of breast cancer. Breast Cancer Res Treat. 2009;115:13–27.

    CAS  PubMed  Google Scholar 

  100. Korkmaz A. Epigenetic actions of melatonin. J Pineal Res. 2009;46:117–8.

    CAS  PubMed  Google Scholar 

  101. Korkmaz A, Tamura H, Manchester LC, Ogden GB, Tan DX, Reiter RJ. Combination of melatonin and a peroxisome proliferator-activated receptor-gamma agonist induces apoptosis in a breast cancer cell line. J Pineal Res. 2009;46:115–6.

    CAS  PubMed  Google Scholar 

  102. Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, et al. Night-shift work and risk of colorectal cancer in the nurses’ health study. J Natl Cancer Inst. 2003;95:825–8.

    Article  PubMed  Google Scholar 

  103. Megdal SP, Kroenke CH, Laden F, Pukkala E, Schernhammer ES. Night work and breast cancer risk: a systematic review and meta-analysis. Eur J Cancer. 2005;41:2023–32.

    PubMed  Google Scholar 

  104. Reiter RJ, Tan DX, Korkmaz A, Erren TC, Piekarski C, Tamura H, et al. Light at night, chronodisruption, melatonin suppression, and cancer risk: a review. Crit Rev Oncog. 2007;13:303–28.

    PubMed  Google Scholar 

  105. Jou MJ, Peng TI, Yu PZ, Jou SB, Reiter RJ, Chen JY, et al. Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis. J Pineal Res. 2007;43:389–403.

    CAS  PubMed  Google Scholar 

  106. Hevia D, Sainz RM, Blanco D, Quiros I, Tan DX, Rodriguez C, et al. Melatonin uptake in prostate cancer cells: intracellular transport versus simple passive diffusion. J Pineal Res. 2008;45:247–57.

    CAS  PubMed  Google Scholar 

  107. Carrillo-Rico A, Guerrero JM, Lundone PJ, Reiter RJ. A review of the multiple actions of melatonin on the immune system. Endocrine. 2005;27:189–200.

    Google Scholar 

  108. Reiter RJ. Melatonin: the chemical expression of darkness. Mol Cell Endocrinol. 1991;79:C153–8.

    CAS  PubMed  Google Scholar 

  109. Tamura H, Nakamura Y, Terron MP, Flores LJ, Manchester LC, Tan DX, et al. Melatonin and pregnancy in the human. Reprod Toxicol. 2008;25:291–303.

    CAS  PubMed  Google Scholar 

  110. Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N et al. Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril. 2008;92:328–43.

    Google Scholar 

  111. Longatti P, Perin A, Rizzo V, Comai S, Giusti P, Costa CV. Ventricular cerebrospinal fluid melatonin concentrations investigated with an endoscopic technique. J Pineal Res. 2007;42:113–8.

    CAS  PubMed  Google Scholar 

  112. Koppisetti S, Jenigiri B, Terron MP, Tengattini S, Tamura H, Flores LJ, et al. Reactive oxygen species and the hypomotility of the gall bladder as targets for the treatment of gallstones with melatonin: a review. Dig Dis Sci. 2008;53:2592–603.

    CAS  PubMed  Google Scholar 

  113. Erren TC, Reiter RJ. A generalized theory of carcinogenesis due to chronodisruption. Neuroendocrinol Lett. 2008;29:815–21.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey

    Ahmet Korkmaz & Turgut Topal

  2. Department of Cellular and Structural Biology, The University of Texas, Health Science Center at San Antonio, Mail Code 7762, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900, USA

    Ahmet Korkmaz, Dun-Xian Tan & Russel J. Reiter

Authors
  1. Ahmet Korkmaz
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  2. Turgut Topal
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  3. Dun-Xian Tan
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  4. Russel J. Reiter
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Correspondence to Russel J. Reiter.

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Korkmaz, A., Topal, T., Tan, DX. et al. Role of melatonin in metabolic regulation. Rev Endocr Metab Disord 10, 261–270 (2009). https://doi.org/10.1007/s11154-009-9117-5

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  • DOI: https://doi.org/10.1007/s11154-009-9117-5

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