Abstract
Combinations of fructose- and fat-rich diets in experimental animals can model the human metabolic syndrome (MS). In rats, the increase in blood pressure (BP) after diet manipulation is sex related and highly dependent on testosterone secretion. However, the extent of the impact of diet on rodent hypophysial-testicular axis remains undefined. In the present study, rats drinking a 10% fructose solution or fed a high-fat (35%) diet for 10 weeks had higher plasma levels of luteinizing hormone (LH) and lower plasma levels of testosterone, without significant changes in circulating follicle-stimulating hormone or the weight of most reproductive organs. Diet manipulation brought about a significant increase in body weight, systolic BP, area under the curve (AUC) of glycemia after an intraperitoneal glucose tolerance test (IPGTT), and plasma low-density lipoprotein cholesterol, cholesterol, triglycerides, and uric acid levels. The concomitant administration of melatonin (25 μg/mL of drinking water) normalized the abnormally high LH levels but did not affect the inhibited testosterone secretion found in fructose- or high-fat-fed rats. Rather, melatonin per se inhibited testosterone secretion. Melatonin significantly blunted the body weight and systolic BP increase, the increase in the AUC of glycemia after an IPGTT, and the changes in circulating lipid profile and uric acid found in both MS models. The results are compatible with a primary inhibition of testicular function in diet-induced MS in rats and with the partial effectiveness of melatonin to counteract the metabolic but not the testicular sequelae of rodent MS.
This research was supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (PICT 2012 0984) and the Universidad de Buenos Aires (M048).
Conflict of interest statement: The author declares no conflict of interest.
References
1. Brown T, Avenell A, Edmunds LD, Moore H, Whittaker V, Avery L, Summerbell C. Systematic review of long-term lifestyle interventions to prevent weight gain and morbidity in adults. Obes Rev 2009;10:627–38.10.1111/j.1467-789X.2009.00641.xSearch in Google Scholar PubMed
2. Garaulet M, Madrid JA. Chronobiology, genetics and metabolic syndrome. Curr Opin Lipidol 2009;20:127–34.10.1097/MOL.0b013e3283292399Search in Google Scholar PubMed
3. Maury E, Ramsey KM, Bass J. Circadian rhythms and metabolic syndrome: from experimental genetics to human disease. Circ Res 2010;106:447–62.10.1161/CIRCRESAHA.109.208355Search in Google Scholar PubMed PubMed Central
4. Tappy L, Le KA, Tran C, Paquot N. Fructose and metabolic diseases: new findings, new questions. Nutrition 2010;26:1044–9.10.1016/j.nut.2010.02.014Search in Google Scholar PubMed
5. Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP. The continuing epidemics of obesity and diabetes in the United States. J Am Med Assoc 2001;286:1195–200.10.1001/jama.286.10.1195Search in Google Scholar PubMed
6. Morley JE. Diabetes and aging: epidemiologic overview. Clin Geriatr Med 2008;24:395–405.10.1016/j.cger.2008.03.005Search in Google Scholar PubMed
7. Riechman SE, Schoen RE, Weissfeld JL, Thaete FL, Kriska AM. Association of physical activity and visceral adipose tissue in older women and men. Obes Res 2002;10:1065–73.10.1038/oby.2002.144Search in Google Scholar PubMed
8. Huffman DM, Barzilai N. Role of visceral adipose tissue in aging. Biochim Biophys Acta 2009;1790:1117–23.10.1016/j.bbagen.2009.01.008Search in Google Scholar PubMed PubMed Central
9. Sepe A, Tchkonia T, Thomou T, Zamboni M, Kirkland JL. Aging and regional differences in fat cell progenitors – a mini-review. Gerontology 2011;57:66–75.10.1159/000279755Search in Google Scholar PubMed PubMed Central
10. Tran LT, Yuen VG, McNeill JH. The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 2009;332: 145–59.10.1007/s11010-009-0184-4Search in Google Scholar PubMed
11. Bremer AA, Stanhope KL, Graham JL, Cummings BP, Wang W, Saville BR, Havel PJ. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes. Clin Transl Sci 2011;4:243–52.10.1111/j.1752-8062.2011.00298.xSearch in Google Scholar PubMed PubMed Central
12. Shimamoto K, Ura N. Mechanisms of insulin resistance in hypertensive rats. Clin Exp Hypertens 2006;28:543–52.10.1080/10641960600851900Search in Google Scholar PubMed
13. Speakman J, Hambly C, Mitchell S, Krol E. The contribution of animal models to the study of obesity. Lab Anim 2008;42: 413–32.10.1258/la.2007.006067Search in Google Scholar PubMed
14. Vasudevan H, Yuen VG, McNeill JH. Testosterone-dependent increase in blood pressure is mediated by elevated Cyp4A expression in fructose-fed rats. Mol Cell Biochem 2012;359:409–18.10.1007/s11010-011-1035-7Search in Google Scholar PubMed
15. Vasudevan H, Nagareddy PR, McNeill JH. Gonadectomy prevents endothelial dysfunction in fructose-fed male rats, a factor contributing to the development of hypertension. Am J Physiol Heart Circ Physiol 2006;291:H3058–64.10.1152/ajpheart.00598.2005Search in Google Scholar PubMed
16. Vasudevan H, Xiang H, McNeill JH. Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Am J Physiol Heart Circ Physiol 2005;289:H1335–42.10.1152/ajpheart.00399.2005Search in Google Scholar PubMed
17. Kamari Y, Peleg E, Leibowitz A, Grossman E. Blunted blood pressure response and elevated plasma adiponectin levels in female Sprague Dawley rats. Am J Hypertens 2012;25:612–9.10.1038/ajh.2011.260Search in Google Scholar PubMed
18. MacDonald AA, Herbison GP, Showell M, Farquhar CM. The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis. Hum Reprod Update 2010;16:293–311.10.1093/humupd/dmp047Search in Google Scholar PubMed
19. Cano P, Jiménez-Ortega V, Larrad A, Toso CF, Cardinali DP, Esquifino AI. Effect of a high-fat diet on 24-h pattern of circulating levels of prolactin, luteinizing hormone, testosterone, corticosterone, thyroid-stimulating hormone and glucose, and pineal melatonin content, in rats. Endocrine 2008; 33:118–25.10.1007/s12020-008-9066-xSearch in Google Scholar PubMed
20. Ribeiro DL, Pinto ME, Maeda SY, Taboga SR, Goes RM. High fat-induced obesity associated with insulin-resistance increases FGF-2 content and causes stromal hyperplasia in rat ventral prostate. Cell Tissue Res 2012;349:577–88.10.1007/s00441-012-1420-xSearch in Google Scholar PubMed
21. Vigueras-Villasenor RM, Rojas-Castaneda JC, Chavez-Saldana M, Gutierrez-Perez O, Garcia-Cruz ME, Cuevas-Alpuche O, Reyes-Romero MM, Zambrano E. Alterations in the spermatic function generated by obesity in rats. Acta Histochem 2011;113:214–20.10.1016/j.acthis.2009.10.004Search in Google Scholar
22. Song D, Arikawa E, Galipeau D, Battell M, McNeill JH. Androgens are necessary for the development of fructose-induced hypertension. Hypertension 2004;43:667–72.10.1161/01.HYP.0000118018.77344.4eSearch in Google Scholar
23. Fernandez CD, Bellentani FF, Fernandes GS, Perobelli JE, Favareto AP, Nascimento AF, Cicogna AC, Kempinas WD. Diet-induced obesity in rats leads to a decrease in sperm motility. Reprod Biol Endocrinol 2011;9:32.10.1186/1477-7827-9-32Search in Google Scholar
24. Balliuzek MF, Grinenko TN, Kvetnaia TV. [The role of melatonin in the development of metabolic syndrome]. Klin Med (Mosk) 2009;87:26–31 [in Russian].Search in Google Scholar
25. Cardinali DP, Cano P, Jimenez-Ortega V, Esquifino AI. Melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology 2011; 93:133–42.10.1159/000324699Search in Google Scholar
26. Kozirog M, Poliwczak AR, Duchnowicz P, Koter-Michalak M, Sikora J, Broncel M. Melatonin treatment improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome. J Pineal Res 2011;50:261–6.10.1111/j.1600-079X.2010.00835.xSearch in Google Scholar
27. Reiter RJ, Tan DX, Korkmaz A, Ma S. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression. Ann Med 2012;44:564–77.10.3109/07853890.2011.586365Search in Google Scholar
28. Nduhirabandi F, Du Toit EF, Lochner A. Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities? Acta Physiol (Oxf) 2012;205:209–23.10.1111/j.1748-1716.2012.02410.xSearch in Google Scholar
29. Dai S, McNeill JH. Fructose-induced hypertension in rats is concentration- and duration-dependent. J Pharmacol Toxicol Methods 1995;33:101–7.10.1016/1056-8719(94)00063-ASearch in Google Scholar
30. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J 2008;22:659–61.10.1096/fj.07-9574LSFSearch in Google Scholar PubMed
31. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Br Med J 1990;300:230–5.10.1136/bmj.300.6719.230Search in Google Scholar PubMed PubMed Central
32. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and reproductive axis: a narrative review. Metabolism 2013;62:457–78.10.1016/j.metabol.2012.08.012Search in Google Scholar
33. Uemura K, Mori N. Influence of age and sex on high-fat diet-induced increase in blood pressure. Nagoya J Med Sci 2006;68:109–14.Search in Google Scholar
34. Sebokova E, Garg ML, Clandinin MT. Modulation of receptor-mediated gonadotropin action in rat testes by dietary fat. Am J Physiol 1988;254:E708–12.10.1152/ajpendo.1988.254.6.E708Search in Google Scholar
35. Gromadzka-Ostrowska J, Przepiorka M, Romanowicz K. Influence of dietary fatty acids composition, level of dietary fat and feeding period on some parameters of androgen metabolism in male rats. Reprod Biol 2002;2:277–93.Search in Google Scholar
36. Lu ZH, Mu YM, Wang BA, Li XL, Lu JM, Li JY, Pan CY, Yanase T, Nawata H. Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell. Biochem Biophys Res Commun 2003;303:1002–7.10.1016/S0006-291X(03)00449-2Search in Google Scholar
37. Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, Muhlbauer E. Melatonin and type 2 diabetes – a possible link? J Pineal Res 2007;42:350–8.10.1111/j.1600-079X.2007.00426.xSearch in Google Scholar PubMed
38. Kanter M, Uysal H, Karaca T, Sagmanligil HO. Depression of glucose levels and partial restoration of pancreatic beta-cell damage by melatonin in streptozotocin-induced diabetic rats. Arch Toxicol 2006;80:362–9.10.1007/s00204-005-0055-zSearch in Google Scholar PubMed
39. Nishida S, Sato R, Murai I, Nakagawa S. Effect of pinealectomy on plasma levels of insulin and leptin and on hepatic lipids in type 2 diabetic rats. J Pineal Res 2003;35:251–6.10.1034/j.1600-079X.2003.00083.xSearch in Google Scholar PubMed
40. Nishida S, Segawa T, Murai I, Nakagawa S. Long-term melatonin administration reduces hyperinsulinemia and improves the altered fatty-acid compositions in type 2 diabetic rats via the restoration of Delta-5 desaturase activity. J Pineal Res 2002;32:26–33.10.1034/j.1600-079x.2002.10797.xSearch in Google Scholar PubMed
41. She M, Deng X, Guo Z, Laudon M, Hu Z, Liao D, Hu X, Luo Y, Shen Q, Su Z, Yin W. NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats. Pharmacol Res 2009;59:248–53.10.1016/j.phrs.2009.01.005Search in Google Scholar PubMed
42. Leibowitz A, Peleg E, Sharabi Y, Shabtai Z, Shamiss A, Grossman E. The role of melatonin in the pathogenesis of hypertension in rats with metabolic syndrome. Am J Hypertens 2008;21:348–51.10.1038/ajh.2007.60Search in Google Scholar PubMed
43. Kitagawa A, Ohta Y, Ohashi K. Melatonin improves metabolic syndrome induced by high fructose intake in rats. J Pineal Res 2011;52:403–13.10.1111/j.1600-079X.2011.00955.xSearch in Google Scholar PubMed
44. Hardeland R, Cardinali DP, Srinivasan V, Spence DW, Brown GM, Pandi-Perumal SR. Melatonin – a pleiotropic, orchestrating regulator molecule. Prog Neurobiol 2011;93:350–84.10.1016/j.pneurobio.2010.12.004Search in Google Scholar
45. Vincent HK, Innes KE, Vincent KR. Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity. Diabetes Obes Metab 2007;9:813–39.10.1111/j.1463-1326.2007.00692.xSearch in Google Scholar
46. Agil A, Navarro-Alarcon M, Ruiz R, Abuhamadah S, El Mir MY, Vazquez GF. Beneficial effects of melatonin on obesity and lipid profile in young Zucker diabetic fatty rats. J Pineal Res 2011;50:207–12.Search in Google Scholar
47. Agil A, Rosado I, Ruiz R, Figueroa A, Zen N, Fernandez-Vazquez G. Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats. J Pineal Res 2012;52:203–10.10.1111/j.1600-079X.2011.00928.xSearch in Google Scholar
48. Prunet-Marcassus B, Desbazeille M, Bros A, Louche K, Delagrange P, Renard P, Casteilla L, Penicaud L. Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity. Endocrinology 2003;144:5347–52.10.1210/en.2003-0693Search in Google Scholar
49. Puchalski SS, Green JN, Rasmussen DD. Melatonin effect on rat body weight regulation in response to high-fat diet at middle age. Endocrine 2003;21:163–7.10.1385/ENDO:21:2:163Search in Google Scholar
50. Sartori C, Dessen P, Mathieu C, Monney A, Bloch J, Nicod P, Scherrer U, Duplain H. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology 2009;150:5311–7.10.1210/en.2009-0425Search in Google Scholar PubMed
51. Rios-Lugo MJ, Cano P, Jimenez-Ortega V, Fernandez-Mateos MP, Scacchi PA, Cardinali DP, Esquifino AI. Melatonin effect on plasma adiponectin, leptin, insulin, glucose, triglycerides and cholesterol in normal and high fat-fed rats. J Pineal Res 2010;49:342–8.10.1111/j.1600-079X.2010.00798.xSearch in Google Scholar PubMed
52. Ladizesky MG, Boggio V, Albornoz LE, Castrillón P, Mautalen CA, Cardinali DP. Melatonin increases oestradiol-induced bone formation in ovariectomized rats. J Pineal Res 2003;34:143–51.10.1034/j.1600-079X.2003.00021.xSearch in Google Scholar PubMed
53. Sanchez-Mateos S, Alonso-Gonzalez C, Gonzalez A, Martinez-Campa CM, Mediavilla MD, Cos S, Sanchez-Barcelo EJ. Melatonin and estradiol effects on food intake, body weight, and leptin in ovariectomized rats. Maturitas 2007;58:91–101.10.1016/j.maturitas.2007.06.006Search in Google Scholar PubMed
54. Hussein MR, Ahmed OG, Hassan AF, Ahmed MA. Intake of melatonin is associated with amelioration of physiological changes, both metabolic and morphological pathologies associated with obesity: an animal model. Int J Exp Pathol 2007;88:19–29.10.1111/j.1365-2613.2006.00512.xSearch in Google Scholar PubMed PubMed Central
55. Raskind MA, Burke BL, Crites NJ, Tapp AM, Rasmussen DD. Olanzapine-induced weight gain and increased visceral adiposity is blocked by melatonin replacement therapy in rats. Neuropsychopharmacology 2007;32:284–8.10.1038/sj.npp.1301093Search in Google Scholar
56. Tan DX, Manchester LC, Fuentes-Broto L, Paredes SD, Reiter RJ. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obes Rev 2011;12:167–88.10.1111/j.1467-789X.2010.00756.xSearch in Google Scholar
57. Roglans N, Sanguino E, Peris C, Alegret M, Vazquez M, Adzet T, Diaz C, Hernandez G, Laguna JC, Sanchez RM. Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha expression and decreased plasma nonesterified fatty acids and liver triglyceride in fructose-fed rats. J Pharmacol Exp Ther 2002;302:232–9.10.1124/jpet.302.1.232Search in Google Scholar
58. Park J, Lemieux S, Lewis GF, Kuksis A, Steiner G. Chronic exogenous insulin and chronic carbohydrate supplementation increase de novo VLDL triglyceride fatty acid production in rats. J Lipid Res 1997;38:2529–36.10.1016/S0022-2275(20)30037-7Search in Google Scholar
59. Cardinali DP, Scacchi Bernasconi PA, Reynoso R, Reyes Toso CF, Scacchi P. Melatonin may curtail the metabolic syndrome: studies on initial and fully established fructose-induced metabolic syndrome in rats. Int J Mol Sci 2013;14:2502–14.10.3390/ijms14022502Search in Google Scholar
60. Kinson GA, Peat F. The influences of illumination, melatonin and pinealectomy on testicular function in the rat. Life Sci I 1971;10:259–69.10.1016/0024-3205(71)90313-4Search in Google Scholar
61. Cardinali DP, Rosner JM. Effects of melatonin, serotonin and N-acetylserotonin on the production of steroids by duck testicular homogenates. Steroids 1971;18:25–37.10.1016/S0039-128X(71)80168-XSearch in Google Scholar
62. Frungieri MB, Mayerhofer A, Zitta K, Pignataro OP, Calandra RS, Gonzalez-Calvar SI. Direct effect of melatonin on Syrian hamster testes: melatonin subtype 1a receptors, inhibition of androgen production, and interaction with the local corticotropin-releasing hormone system. Endocrinology 2005;146:1541–52.10.1210/en.2004-0990Search in Google Scholar PubMed
63. Rossi SP, Matzkin ME, Terradas C, Ponzio R, Puigdomenech E, Levalle O, Calandra RS, Frungieri MB. New insights into melatonin/CRH signaling in hamster Leydig cells. Gen Comp Endocrinol 2012;178:153–63.10.1016/j.ygcen.2012.04.031Search in Google Scholar PubMed
64. Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, Zisapel N. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med 2010;8:51.10.1186/1741-7015-8-51Search in Google Scholar PubMed PubMed Central
65. Wright J, Aldhous M, Franey C, English J, Arendt J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf) 1986;24:375–82.10.1111/j.1365-2265.1986.tb01641.xSearch in Google Scholar PubMed
66. Waldhauser F, Lieberman HR, Lynch HJ, Waldhauser M, HerknerK, Frisch H, Vierhapper H, Waldhausl W, Schemper M, Wurtman RJ. A pharmacological dose of melatonin increases PRL levels in males without altering those of GH, LH, FSH, TSH, testosterone or cortisol. Neuroendocrinology 1987;46:125–30.10.1159/000124808Search in Google Scholar PubMed
67. Luboshitzky R, Levi M, Shen-Orr Z, Blumenfeld Z, Herer P, Lavie P. Long-term melatonin administration does not alter pituitary-gonadal hormone secretion in normal men. Hum Reprod 2000;15:60–5.10.1093/humrep/15.1.60Search in Google Scholar PubMed
68. Mero AA, Vahalummukka M, Hulmi JJ, Kallio P, von Wright A. Effects of resistance exercise session after oral ingestion of melatonin on physiological and performance responses of adult men. Eur J Appl Physiol 2006;96:729–39.10.1007/s00421-005-0119-zSearch in Google Scholar PubMed
69. Jimenez-Ortega V, Cano P, Pagano ES, Fernández-Mateos P, Esquifino AI, Cardinali DP. Melatonin supplementation decreases prolactin synthesis and release in rat adenohypophysis. Correlation with anterior pituitary redox state and circadian clock mechanisms. Chronobiol Int 2012;29:1021–35.10.3109/07420528.2012.705936Search in Google Scholar PubMed
70. Bartness TJ, Powers JB, Hastings MH, Bittman EL, Goldman BD. The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception, and the photoperiodic control of seasonal responses? J Pineal Res 1993;15:161–90.10.1111/j.1600-079X.1993.tb00903.xSearch in Google Scholar PubMed
71. Bittman EL, Karsch FJ. Nightly duration of pineal melatonin secretion determines the reproductive response to inhibitory day length in the ewe. Biol Reprod 1984;30:585–93.10.1095/biolreprod30.3.585Search in Google Scholar PubMed
72. Nakagawa T, Cirillo P, Sato W, Gersch M, Sautin Y, Roncal C, Mu W, Sanchez-Lozada LG, Johnson RJ. The conundrum of hyperuricemia, metabolic syndrome, and renal disease. Intern Emerg Med 2008;3:313–8.10.1007/s11739-008-0141-3Search in Google Scholar PubMed PubMed Central
73. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ. Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 2001;38:1101–6.10.1161/hy1101.092839Search in Google Scholar PubMed
74. Sanchez-Lozada LG, Tapia E, Santamaria J, Avila-Casado C, Soto V, Nepomuceno T, Rodriguez-Iturbe B, Johnson RJ, Herrera-Acosta J. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int 2005;67:237–47.10.1111/j.1523-1755.2005.00074.xSearch in Google Scholar PubMed
75. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci USA 2009;106:4453–8.10.1073/pnas.0808180106Search in Google Scholar PubMed PubMed Central
76. Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, Britton TC, Crowe C, Dijk DJ, Espie CA, Gringras P, Hajak G, Idzikowski C, Krystal AD, Nash JR, Selsick H, Sharpley AL, Wade AG. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 2010;24:1577–601.10.1177/0269881110379307Search in Google Scholar PubMed
77. Tutuncu NB, Batur MK, Yildirir A, Tutuncu T, Deger A, Koray Z, Erbas B, Kabakci G, Aksoyek S, Erbas T. Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy. J Pineal Res 2005;39:43–9.10.1111/j.1600-079X.2005.00213.xSearch in Google Scholar PubMed
78. Dietrich K, Birkmeier S, Schleinitz D, Breitfeld J, Enigk B, Muller I, Bottcher Y, Lindner T, Stumvoll M, Tonjes A, Kovacs P. Association and evolutionary studies of the melatonin receptor 1B gene (MTNR1B) in the self-contained population of Sorbs from Germany. Diabet Med 2011;28:1373–80.10.1111/j.1464-5491.2011.03374.xSearch in Google Scholar PubMed
79. Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, Loos RJ, Manning AK, Jackson AU, Aulchenko Y, Potter SC, Erdos MR, Sanna S, Hottenga JJ, Wheeler E, Kaakinen M, Lyssenko V, Chen WM, Ahmadi K, Beckmann JS, Bergman RN, Bochud M, Bonnycastle LL, Buchanan TA, Cao A, Cervino A, Coin L, Collins FS, Crisponi L, de Geus EJ, Dehghan A, Deloukas P, Doney AS, Elliott P, Freimer N, Gateva V, Herder C, Hofman A, Hughes TE, Hunt S, Illig T, Inouye M, Isomaa B, Johnson T, Kong A, Krestyaninova M, Kuusisto J, Laakso M, Lim N, Lindblad U, Lindgren CM, McCann OT, Mohlke KL, Morris AD, Naitza S, Orru M, Palmer CN, Pouta A, Randall J, Rathmann W, Saramies J, Scheet P, Scott LJ, Scuteri A, Sharp S, Sijbrands E, Smit JH, Song K, Steinthorsdottir V, Stringham HM, Tuomi T, Tuomilehto J, Uitterlinden AG, Voight BF, Waterworth D, Wichmann HE, Willemsen G, Witteman JC, Yuan X, Zhao JH, Zeggini E, Schlessinger D, Sandhu M, Boomsma DI, Uda M, Spector TD, Penninx BW, Altshuler D, Vollenweider P, Jarvelin MR, Lakatta E, Waeber G, Fox CS, Peltonen L, Groop LC, Mooser V, Cupples LA, Thorsteinsdottir U, Boehnke M, Barroso I, Van Duijn C, Dupuis J, Watanabe RM, Stefansson K, McCarthy MI, Wareham NJ, Meigs JB, Abecasis GR. Variants in MTNR1B influence fasting glucose levels. Nat Genet 2009;41:77–81.10.1038/ng.290Search in Google Scholar PubMed PubMed Central
80. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, Lindgren CM, Magi R, Morris AP, Randall J, Johnson T, Elliott P, Rybin D, Thorleifsson G, Steinthorsdottir V, Henneman P, Grallert H, Dehghan A, Hottenga JJ, Franklin CS, Navarro P, Song K, Goel A, Perry JR, Egan JM, Lajunen T, Grarup N, Sparso T, Doney A, Voight BF, Stringham HM, Li M, Kanoni S, Shrader P, Cavalcanti-Proenca C, Kumari M, Qi L, Timpson NJ, Gieger C, Zabena C, Rocheleau G, Ingelsson E, An P, O’Connell J, Luan J, Elliott A, McCarroll SA, Payne F, Roccasecca RM, Pattou F, Sethupathy P, Ardlie K, Ariyurek Y, Balkau B, Barter P, Beilby JP, Ben Shlomo Y, Benediktsson R, Bennett AJ, Bergmann S, Bochud M, Boerwinkle E, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Bottcher Y, Brunner E, Bumpstead SJ, Charpentier G, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Cornelis M, Crawford G, Crisponi L, Day IN, de Geus EJ, Delplanque J, Dina C, Erdos MR, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Fox CS, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Groves CJ, Grundy S, Gwilliam R, Gyllensten U, Hadjadj S, Hallmans G, Hammond N, Han X, Hartikainen AL, Hassanali N, Hayward C, Heath SC, Hercberg S, Herder C, Hicks AA, Hillman DR, Hingorani AD, Hofman A, Hui J, Hung J, Isomaa B, Johnson PR, Jorgensen T, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Lyssenko V, Mahley R, Mangino M, Manning AK, Martinez-Larrad MT, McAteer JB, McCulloch LJ, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Morken MA, Mukherjee S, Naitza S, Narisu N, Neville MJ, Oostra BA, Orru M, Pakyz R, Palmer CN, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rathmann W, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Roden M, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Scott LJ, Seedorf U, Sharp SJ, Shields B, Sigurethsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvanen AC, Tanaka T, Thorand B, Tichet J, Tonjes A, Tuomi T, Uitterlinden AG, van Dijk KW, van Hoek M, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Walters GB, Ward KL, Watkins H, Weedon MN, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zeggini E, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Hattersley AT, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Rios M, Morris AD, Lind L, Palmer LJ, Hu FB, Franks PW, Ebrahim S, Marmot M, Kao WH, Pankow JS, Sampson MJ, Kuusisto J, Laakso M, Hansen T, Pedersen O, Pramstaller PP. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010;42:105–16.10.1038/ng.520Search in Google Scholar PubMed PubMed Central
81. Tamura H, Nakamura Y, Narimatsu A, Yamagata Y, Takasaki A, Reiter RJ, Sugino N. Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels. J Pineal Res 2008;45:101–5.10.1111/j.1600-079X.2008.00561.xSearch in Google Scholar PubMed
82. Shatilo VB, Bondarenko EV, Antoniuk-Shcheglova IA. [Metabolic disorders in elderly patients with hypertension and their correction with melatonin]. Adv Gerontol 2012;25:84–9.Search in Google Scholar
83. Weishaupt JH, Bartels C, Polking E, Dietrich J, Rohde G, Poeggeler B, Mertens N, Sperling S, Bohn M, Huther G, Schneider A, Bach A, Siren AL, Hardeland R, Bahr M, Nave KA, Ehrenreich H. Reduced oxidative damage in ALS by high-dose enteral melatonin treatment. J Pineal Res 2006;41:313–23.10.1111/j.1600-079X.2006.00377.xSearch in Google Scholar PubMed
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Mini Review Article
- Beneficial effect of melatonin treatment on age-related insulin resistance and on the development of type 2 diabetes
- Review Articles
- Natural products and the aging process
- Role of oestrogens on oxidative stress and inflammation in ageing
- Hormesis and vitagenes in aging and longevity: mitochondrial control and hormonal regulation
- Original Articles
- Early gender differences in the redox status of the brain mitochondria with age: effects of melatonin therapy
- Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis
Articles in the same Issue
- Mini Review Article
- Beneficial effect of melatonin treatment on age-related insulin resistance and on the development of type 2 diabetes
- Review Articles
- Natural products and the aging process
- Role of oestrogens on oxidative stress and inflammation in ageing
- Hormesis and vitagenes in aging and longevity: mitochondrial control and hormonal regulation
- Original Articles
- Early gender differences in the redox status of the brain mitochondria with age: effects of melatonin therapy
- Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis