Abstract
Melatonin is a hormone secreted by the pineal gland under the control of the circadian rhythm, and is released in the dark and suppressed during the day. In the past decades, melatonin has been considered to be used in the treatment for diabetes mellitus (DM). This is due to a functional inter-relationship between melatonin and insulin. Elevated oxidative stress is a feature found in DM associated with diabetic neuropathy (DN), retinopathy (DR), nephropathy and cardiovascular disease. Reactive oxygen species (ROS) and nitrogen oxidative species (NOS) are usually produced in massive amounts via glucose and lipid peroxidation, and this leads to diabetic complications. At the molecular level, ROS causes damage to the biomolecules and triggers apoptosis. Melatonin, as an antioxidant and a free radical scavenger, ameliorates oxidative stress caused by ROS and NOS. Besides that, melatonin administration is proven to bring other anti-DM effects such as reducing cellular apoptosis and promoting the production of antioxidants.
Author statement
Author contributions: JXM and JHO wrote the manuscript, and KYN and RYK critically reviewed the manuscript. SMC formulated the entire concept and reviewed the manuscript.
Research funding: None declared.
Conflict of interest: None declared.
Informed consent: Not applicable.
Ethical approval: Not applicable.
References
[1] You W, Henneberg M. Type 1 diabetes prevalence increasing globally and regionally: the role of natural selection and life expectancy at birth. BMJ Open Diabetes Res Care. 2016;4:1–7.10.1136/bmjdrc-2015-000161Suche in Google Scholar PubMed PubMed Central
[2] Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world – a growing challenge. N Engl J Med. 2007;356:213–5.10.1056/NEJMp068177Suche in Google Scholar PubMed
[3] Prasad RB, Groop L. Genetics of type 2 diabetes-pitfalls and possibilities. Genes. 2015;6:87–123.10.3390/genes6010087Suche in Google Scholar PubMed PubMed Central
[4] Wu Y, Ding Y, Tanaka Y, Zhang W. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. Int J Med Sci. 2014;11:1185–200.10.7150/ijms.10001Suche in Google Scholar PubMed PubMed Central
[5] Bondeva T, Wolf G. Reactive oxygen species in diabetic nephropathy: friend or foe ? Nephrol Dial Transplant. 2014;29:1998–2003.10.1093/ndt/gfu037Suche in Google Scholar PubMed
[6] Yan SF, Ramasamy R, Schmidt AM. Mechanisms of disease: advanced glycation end-products and their receptor in inflammation and diabetes complications. Nat Clin Pract. 2008;4:285–93.10.1038/ncpendmet0786Suche in Google Scholar PubMed
[7] Yamagishi S. Role of advanced glycation end products (AGEs) and receptor for AGEs (RAGE) in vascular damage in diabetes. Exp Gerontol. 2011;46:217–24.10.1016/j.exger.2010.11.007Suche in Google Scholar PubMed
[8] Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review on the role of antioxidants in the management of diabetes and its complications. Biomed Pharmacother. 2005;59:365–73.10.1016/j.biopha.2005.07.002Suche in Google Scholar PubMed
[9] Mayo JC, Tan D, Sainz RM, Alatorre-jimenez M. Melatonin as an antioxidant: under promises but over delivers. J Pineal Res. 2016;61:253–78.10.1111/jpi.12360Suche in Google Scholar PubMed
[10] Wang J, Wang H. Oxidative stress in pancreatic beta cell regeneration. Oxid Med Cell Longev. 2017;2017:1930261.10.1155/2017/1930261Suche in Google Scholar PubMed PubMed Central
[11] Chattoraj A, Liu T. Melatonin formation in mammals: in vivo perspectives. Rev Endocr Metab Disord. 2009;10:237–43.10.1007/s11154-009-9125-5Suche in Google Scholar PubMed PubMed Central
[12] Devavry S, Legros C, Brasseur C, Cohen W, Guenin SP, Delagrange P, et al. Molecular pharmacology of the mouse melatonin receptors MT1and MT2. Eur J Pharmacol. 2012;677:15–21.10.1016/j.ejphar.2011.12.009Suche in Google Scholar PubMed
[13] McMullan CJ, Schernhammer ES, Rimm EB, Hu FB, Forman JP. Melatonin secretion and the incidence of type 2 diabetes. J Am Med Assoc. 2013;309:1388–96.10.1001/jama.2013.2710Suche in Google Scholar PubMed PubMed Central
[14] Vanecek J. Cellular mechanisms of melatonin action. Physiol Rev. 1998;78:687–721.10.1152/physrev.1998.78.3.687Suche in Google Scholar PubMed
[15] Tan HY, Ng KY, Koh RY, Chye SM. Pharmacological effects of melatonin as neuroprotectant in rodent model: a review on the current biological evidence. Cell Mol Neurobiol. 2019.10.1007/s10571-019-00724-1Suche in Google Scholar PubMed
[16] She M, Laudon M, Yin W. Melatonin receptors in diabetes: a potential new therapeutical target? Eur J Pharmacol. 2015;744:220–3.10.1016/j.ejphar.2014.08.012Suche in Google Scholar PubMed
[17] Mulder H. Melatonin signalling and type 2 diabetes risk: too little, too much or just right? Diabetologia. 2017;60:826–9.10.1007/s00125-017-4249-8Suche in Google Scholar PubMed
[18] Peschke E, Bähr I, Mühlbauer E. Melatonin and pancreatic islets: interrelationships between melatonin, insulin and glucagon. Int J Mol Sci. 2013;14:6981–7015.10.3390/ijms14046981Suche in Google Scholar PubMed PubMed Central
[19] Peschke E, Bach AG, Mühlbauer E. Parallel signaling pathways of melatonin in the pancreatic β-cell. J Pineal Res. 2006;40:184–91.10.1111/j.1600-079X.2005.00297.xSuche in Google Scholar PubMed
[20] 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;13:1025–32.10.1046/j.1365-2826.2001.00717.xSuche in Google Scholar PubMed
[21] Singh M, Jadhav HR. Melatonin: functions and ligands. Drug Discov Today. 2014;19:1410–8.10.1016/j.drudis.2014.04.014Suche in Google Scholar PubMed
[22] Nagorny CL, Sathanoori R, Voss U, Mulder H, Wierup N. Distribution of melatonin receptors in murine pancreatic islets. J Pineal Res. 2011;50:412–7.10.1111/j.1600-079X.2011.00859.xSuche in Google Scholar PubMed
[23] Picinato MC, Hirata AE, Cipolla-Neto J, Curi R, Carvalho CR, Anhê GF, et al. Activation of insulin and IGF-1 signaling pathways by melatonin through MT1 receptor in isolated rat pancreatic islets. J Pineal Res. 2008;44:88–94.10.1111/j.1600-079X.2007.00493.xSuche in Google Scholar PubMed
[24] Akmali M, Ahmadi R, Vessal M. Pre- and post-treatment of streptozocin administered rats with melatonin: effects on some hepatic enzymes of carbohydrate metabolism. Arch Iran Med. 2010;13:105–10.Suche in Google Scholar PubMed
[25] Fonken LK, Nelson RJ. The effects of light at night on circadian clocks and metabolism. Endocr Rev. 2014;35:648–70.10.1210/er.2013-1051Suche in Google Scholar PubMed
[26] Greenhill C. Risk factors: melatonin signalling implicated in the risk of T2DM. Nat Rev Endocrinol. 2016;12:374.10.1038/nrendo.2016.85Suche in Google Scholar PubMed
[27] 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;40:135–43.10.1111/j.1600-079X.2005.00287.xSuche in Google Scholar PubMed
[28] Cavalcanti-proenc C, Bouatia-naji N, Sparso T, Rocheleau G, Holmkvist J, Marchand M, et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet. 2009;41:89–94.10.1038/ng.277Suche in Google Scholar PubMed
[29] Karamitri A, Jockers R. Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol [Internet]. 2019;15:105–25.10.1038/s41574-018-0130-1Suche in Google Scholar PubMed
[30] Jonsson A, Ladenvall C, Ahluwalia TS, Kravic J, Krus U, Taneera J, et al. Effects of common genetic variants associated with type 2 diabetes and glycemic traits on α- and β-cell function and insulin action in humans. Diabetes. 2013;62:2978–83.10.2337/db12-1627Suche in Google Scholar PubMed PubMed Central
[31] Walford GA, Green T, Neale B, Isakova T, Rotter JI, Grant SF, et al. Common genetic variants differentially influence the transition from clinically defined states of fasting glucose metabolism. Diabetologia. 2012;55:331–9.10.1007/s00125-011-2353-8Suche in Google Scholar PubMed PubMed Central
[32] Tuomi T, Nagorny CL, Singh P, Bennet H, Yu Q, Alenkvist I, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab. 2016;23:1067–77.10.1016/j.cmet.2016.04.009Suche in Google Scholar PubMed
[33] Gaulton KJ, Ferreira T, Lee Y, Raimondo A, Mägi R, Reschen ME, et al. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. Nat Genet. 2015;47:1415–25.10.1038/ng.3437Suche in Google Scholar PubMed PubMed Central
[34] Karamitri A, Renault N, Clement N, Guillaume JL, Jockers R. Minireview: toward the establishment of a link between melatonin and glucose homeostasis: association of melatonin MT2 receptor variants with type 2 diabetes. Mol Endocrinol. 2013;27:1217–33.10.1210/me.2013-1101Suche in Google Scholar PubMed PubMed Central
[35] Yeǧin ZA, Mutluay R, Elbeg Ş, Karakuş R, Çakir N. The impact of melatonin on glucose homeostasis. Turkish J Endocrinol Metab. 2009;13:52–5.Suche in Google Scholar
[36] Prokopenko I, Langenberg C, Florez JC, Saxena R, Soranzo N, Thorleifsson G, et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet. 2009;41:77–81.10.1038/ng.290Suche in Google Scholar PubMed PubMed Central
[37] Peschke E, Stumpf I, Bazwinsky I, Litvak L, Dralle H, Mühlbauer E. Melatonin and type 2 diabetes – a possible link? J Pineal Res. 2007;42:350–8.10.1111/j.1600-079X.2007.00426.xSuche in Google Scholar PubMed
[38] Mulder H, Nagorny CL, Lyssenko V, Groop L. Melatonin receptors in pancreatic islets: good morning to a novel type 2 diabetes gene. Diabetologia. 2009;52:1240–9.10.1007/s00125-009-1359-ySuche in Google Scholar PubMed
[39] Agil A, Rosado I, Ruiz R, Figueroa A, Zen N, Fernández-Vázquez 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.xSuche in Google Scholar PubMed
[40] 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.Suche in Google Scholar PubMed
[41] Peschke E, Hofmann K, Bähr I, Streck S, Albrecht E, Wedekind D, et al. The insulin-melatonin antagonism: studies in the LEW.1AR1-iddm rat (an animal model of human type 1 diabetes mellitus). Diabetologia. 2011;54:1831–40.10.1007/s00125-011-2138-0Suche in Google Scholar PubMed
[42] Peschke E, Wolgast S, Bazwinsky I, Pönicke K, Muhlbauer E. Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes. J Pineal Res. 2008;45:439–48.10.1111/j.1600-079X.2008.00612.xSuche in Google Scholar PubMed
[43] Owino S, Contreras-Alcantara S, Baba K, Tosini G. Melatonin signaling controls the daily rhythm in blood glucose levels independent of peripheral clocks. PLoS One. 2016;11:1–16.10.1371/journal.pone.0148214Suche in Google Scholar PubMed PubMed Central
[44] 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 Metab. 2017;275:E934–41.10.1152/ajpendo.1998.275.6.E934Suche in Google Scholar PubMed
[45] Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination. J Pineal Res. 2011;51:1–16.10.1111/j.1600-079X.2011.00916.xSuche in Google Scholar PubMed
[46] Kdziora-Kornatowska K, Szewczyk-Golec K, Kozakiewicz M, Pawluk H, Czuczejko J, Kornatowski T, et al. Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients. J Pineal Res. 2009;46(3):333–7.10.1111/j.1600-079X.2009.00666.xSuche in Google Scholar PubMed
[47] Mayo JC, Sainz RM, Antolín I, Herrera F, Martin V, Rodriguez C. Melatonin regulation of antioxidant enzyme gene expression. Cell Mol Life Sci. 2002;59:1706–13.10.1007/PL00012498Suche in Google Scholar PubMed
[48] Hadjzadeh MA, Alikhani V, Hosseinian S, Zarei B, Keshavarzi Z. The effect of melatonin against gastric oxidative stress and dyslipidemia in streptozotocin-induced diabetic rats. Acta Endocrinol (Buchar). 2018;14:453–8.10.4183/aeb.2018.453Suche in Google Scholar PubMed PubMed Central
[49] Luhinich N, Gerush I. Effects of 7-day melatonin introduction on the hydrogen sulfide production and glutathione system in the liver of alloxan induced diabetic rats. Georg Med News. 2019;289:135–9.Suche in Google Scholar
[50] Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107:1058–70.10.1161/CIRCRESAHA.110.223545Suche in Google Scholar PubMed PubMed Central
[51] Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.10.1038/414813aSuche in Google Scholar PubMed
[52] Zephy D, Ahmad J. Type 2 diabetes mellitus: role of melatonin and oxidative stress. Diabetes Metab Syndr. 2015;9:127–31.10.1016/j.dsx.2014.09.018Suche in Google Scholar PubMed
[53] Wan XD, Li SQ, Xi SM, Wang JF, Guo YC, Wang XM. Long-term melatonin administration improves glucose homeostasis and insulin resistance state in high-fat diet fed rats. Cent Eur J Biol. 2013;8:958–67.10.2478/s11535-013-0211-zSuche in Google Scholar
[54] Lo CC, Lin SH, Chang JS, Chien YW. Effects of melatonin on glucose homeostasis, antioxidant ability, and adipokine secretion in ICR mice with NA/STZ-induced hyperglycemia. Nutrients. 2017;9:1187–200.10.3390/nu9111187Suche in Google Scholar PubMed PubMed Central
[55] Rybka J, Kędziora-kornatowska K, Kupczyk D, Muszalik M, Kornatowski M, Kędziora J. Antioxidant effect of immediate- versus sustained-release melatonin in type 2 diabetes mellitus and healthy controls. Drug Deliv. 2016;23:814.10.3109/10717544.2014.917343Suche in Google Scholar PubMed
[56] Bonnefond A, Froguel P. The case for too little melatonin signalling in increased diabetes risk. Diabetologia. 2017;60:823–5.10.1007/s00125-017-4255-xSuche in Google Scholar PubMed
[57] Amaral FG, Turati AO, Barone M, Scialfa JH, Do Carmo Buonfiglio D, Peres R, et al. Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia. J Pineal Res. 2014;57:67–79.10.1111/jpi.12144Suche in Google Scholar PubMed
[58] Sharma S, Singh H, Ahmad N, Mishra P, Tiwari A. The role of melatonin in diabetes: therapeutic implications. Arch Endocrinol Metab. 2015;59:391–9.10.1590/2359-3997000000098Suche in Google Scholar PubMed
[59] Sartori C, Dessen P, Mathieu C, Monney A, Bloch J, Nicod P, et al. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology. 2009;150:5311–7.10.1210/en.2009-0425Suche in Google Scholar PubMed
[60] de Oliveira AC, Andreotti S, Farias Tda S, Torres-Leal FL, De Proença AR, Campaña AB, et al. Metabolic disorders and adipose tissue insulin responsiveness in neonatally STZ-induced diabetic rats are improved by long-term melatonin treatment. Endocrinology. 2012;153:2178–88.10.1210/en.2011-1675Suche in Google Scholar PubMed
[61] de Oliveira AC, Andreotti S, Sertie RA, Campana AB, de Proença AR, Vasconcelos RP, et al. Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats. Life Sci. 2018;199:158–66.10.1016/j.lfs.2018.02.040Suche in Google Scholar PubMed
[62] Bundhun PK, Bhurtu A, Yuan J. Impact of type 2 diabetes mellitus on the long-term mortality in patients who were treated by coronary artery bypass surgery. Med (Baltimore). 2017;96:e7022.10.1097/MD.0000000000007022Suche in Google Scholar PubMed PubMed Central
[63] Rathmann W, Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27:2568–9.10.2337/diacare.27.10.2568Suche in Google Scholar PubMed
[64] Raygan F, Ostadmohammadi V, Bahmani F, Reiter RJ, Asemi Z. Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2019;38:191–6.10.1016/j.clnu.2017.12.004Suche in Google Scholar PubMed
[65] Boudina S, Abel ED. Diabetic cardiomyopathy, causes and effects. Rev Endocr Metab Disord. 2010;11:31–9.10.1007/s11154-010-9131-7Suche in Google Scholar PubMed PubMed Central
[66] Zhou H, Yue Y, Wang J, Ma Q, Chen Y. Melatonin therapy for diabetic cardiomyopathy: a mechanism involving Syk-mitochondrial complex I-SERCA pathway. Cell Signal. 2018;47:88–100.10.1016/j.cellsig.2018.03.012Suche in Google Scholar PubMed
[67] Amin AH, El-Missiry MA, Othman Al. Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes induced apoptosis. Eur J Pharmacol. 2014;747(December):166–73.10.1016/j.ejphar.2014.12.002Suche in Google Scholar PubMed
[68] Ouyang C, You J, Xie Z. The interplay between autophagy and apoptosis in the diabetic heart. J Mol Cell Cardiol. 2014;71:71–80.10.1016/j.yjmcc.2013.10.014Suche in Google Scholar PubMed
[69] Xiong FY, Tang ST, Su H, Tang HQ, Jiang P, Zhou Q, et al. Melatonin ameliorates myocardial apoptosis by suppressing endoplasmic reticulum stress in rats with long – term diabetic cardiomyopathy. Mol Med Rep. 2018;17:374–81.10.3892/mmr.2017.7841Suche in Google Scholar PubMed
[70] Wang W, Wang W, Azadzoi KM, Dai P, Wang Q, Sun J, et al. Alu RNA accumulation in hyperglycemia augments oxidative stress and impairs eNOS and SOD2 expression in endothelial cells. Mol Cell Endocrinol. 2016;426:91–100.10.1016/j.mce.2016.02.008Suche in Google Scholar PubMed
[71] Li C, Lv L, Li H, Yu D. Cardiac fibrosis and dysfunction in experimental diabetic cardiomyopathy are ameliorated by alpha-lipoic acid. Cardiovasc Diabetol. 2012;11:1–10.10.1186/1475-2840-11-73Suche in Google Scholar PubMed PubMed Central
[72] Salmanoglu DS, Gurpinar T, Vural K, Ekerbicer N, Darıverenli E, Var A. Melatonin and L-carnitin improves endothelial disfunction and oxidative stress in type 2 diabetic rats. Redox Biol. 2016;8:199–204.10.1016/j.redox.2015.11.007Suche in Google Scholar PubMed PubMed Central
[73] Manchester LC, Coto-Montes A, Boga JA, Andersen LP, Zhou Z, Galano A, et al. Melatonin: an ancient molecule that makes oxygen metabolically tolerable. J Pineal Res. 2015;59:403–19.10.1111/jpi.12267Suche in Google Scholar PubMed
[74] Kandemir YB, Tosun V, Güntekin Ü. Melatonin protects against streptozotocin-induced diabetic cardiomyopathy through the mammalian target of rapamycin (mTOR) signaling pathway. Adv Clin Exp Med. 2019;28:1171–7.10.17219/acem/103799Suche in Google Scholar PubMed
[75] Behram Kandemir Y, Guntekin Ü, Tosun V, Korucuk N, Bozdemir MN. Melatonin protects against streptozotocin-induced diabetic cardiomyopathy by the phosphorylation of vascular endothelial growth factor-A (VEGF-A). Cell Mol Biol (Noisy-le-grand). 2018;64:47–52.10.14715/cmb/2018.64.14.8Suche in Google Scholar PubMed
[76] Dal B, Francisco S, Parente EB, Carolina A, Campos N, Cury AN, et al. Hyperglycemia effect on coronary disease in patients with metabolic syndrome evaluated by intracoronary ultrasonography. PLoS One 2017;12:1–9.10.1371/journal.pone.0171733Suche in Google Scholar
[77] Michaelson J, Hariharan V, Huang H. Hyperglycemic and hyperlipidemic conditionsalter cardiac cell biomechanical properties. Biophys J. 2014;106:2322–9.10.1016/j.bpj.2014.04.040Suche in Google Scholar PubMed PubMed Central
[78] Kwong B, Tan H, Hong C, Natesan P. Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats. Life Sci. 2005;76:2827–39.10.1016/j.lfs.2004.10.051Suche in Google Scholar PubMed
[79] 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;50:207–12.10.1111/j.1600-079X.2010.00830.xSuche in Google Scholar PubMed
[80] Tengattini S, Russel J, Tan D, Pilar M, Rodella LF. Cardiovascular diseases: protective effects of melatonin. J Pineal Res. 2008;44:16–25.10.1111/j.1600-079X.2007.00518.xSuche in Google Scholar PubMed
[81] Mehmeti I, Lenzen S, Lortz S. Modulation of Bcl-2-related protein expression in pancreatic beta cells by pro-inflammatory cytokines and its dependence on the antioxidative defense status. Mol Cell Endocrinol. 2011;332:88–96.10.1016/j.mce.2010.09.017Suche in Google Scholar PubMed
[82] Baydas G, Reiter RJ, Akbulut M, Tuzcu M, Tamer S. Melatonin inhibits neural apoptosis induced by homocysteine in hippocampus of rats via inhibition of cytochrome c translocation and caspase-3 activation and by regulating pro- and anti-apoptotic protein levels. Neuroscience. 2005;135:879–86.10.1016/j.neuroscience.2005.05.048Suche in Google Scholar PubMed
[83] Yu L, Liang H, Lu Z, Zhao G, Zhai M, Yang Y, et al. Membrane receptor-dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia-reperfusion injury: in vivo and in vitro studies. J Pineal Res. 2015;59:420–33.10.1111/jpi.12272Suche in Google Scholar PubMed
[84] Yu L, Liang H, Dong X, Zhao G, Jin Z, Zhai M, et al. Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin. J Pineal Res. 2015;59:376–90.10.1111/jpi.12269Suche in Google Scholar PubMed
[85] Yu L, Di W, Dong X, Li Z, Zhang Y, Xue X, et al. Melatonin protects diabetic heart against ischemia-reperfusion injury, role of membrane receptor-dependent cGMP-PKG activation. BBA – Mol Basis Dis. 2018;1864:563–78.10.1016/j.bbadis.2017.11.023Suche in Google Scholar PubMed
[86] Tang S, Su H, Zhang Q, Tang H, Wang C, Zhou Q, et al. Melatonin attenuates aortic endothelial permeability and arteriosclerosis in streptozotocin-induced diabetic rats: possible role of MLCK- and MLCP-dependent MLC phosphorylation. J Cardiovasc Pharmacol Ther. 2016;21:82–92.10.1177/1074248415583090Suche in Google Scholar PubMed
[87] Ding M, Feng N, Tang D, Feng J, Li Z, Jia M, et al. Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through SIRT1-PGC1α pathway. J Pineal Res. 2018;65:e12491.10.1111/jpi.12491Suche in Google Scholar PubMed PubMed Central
[88] Mariappan N, Elks CM, Sriramula S, Guggilam A, Liu Z, Borkhsenious O, et al. NF-kappa B-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes. Cardiovasc Res. 2010;85:473–83.10.1093/cvr/cvp305Suche in Google Scholar PubMed PubMed Central
[89] Verma SK, Garikipati VN, Kishore R. Mitochondrial dysfunction and its impact on diabetic heart. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1098–105.10.1016/j.bbadis.2016.08.021Suche in Google Scholar PubMed PubMed Central
[90] Wang S, Zhao Z, Feng X, Cheng Z, Xiong Z, Wang T, et al. Melatonin activates Parkin translocation and rescues the impaired mitophagy activity of diabetic cardiomyopathy through Mst1 inhibition. J Cell Mol Med. 2018;22:5132–44.10.1111/jcmm.13802Suche in Google Scholar PubMed PubMed Central
[91] Hu J, Wang T, Man W, Yin T, Guo W, Gao E, et al. Melatonin protects against diabetic cardiomyopathy through Mst1/Sirt3 signaling. J Pineal Res. 2017;63:1–13.10.1111/jpi.12418Suche in Google Scholar
[92] Rangasamy S, Mcguire PG, Das A. Diabetic retinopathy and inflammation: novel therapeutic targets. Middle East Afr J Ophthalmol. 2012;19:52–29.10.4103/0974-9233.92116Suche in Google Scholar PubMed PubMed Central
[93] Mitsuhashi J, Morikawa S, Shimizu K, Ezaki T, Yasuda Y. Intravitreal injection of erythropoietin protects against retinal vascular regression at the early stage of diabetic retinopathy in streptozotocin-induced diabetic rats. Exp Eye Res. 2013;106:64–73.10.1016/j.exer.2012.11.001Suche in Google Scholar PubMed
[94] Masoud RE. Prevention of diabetic retinopathy by melatonin in rats with STZ induced diabetes mellitus. Int J Sci Res. 2017;6:843–7.Suche in Google Scholar
[95] Gundogan FC, Yolcu U, Akay F, Ilhan A, Ozge G, Uzun S. Diabetic macular edema. Pak J Med Sci. 2016;32:505–10.10.12669/pjms.322.8496Suche in Google Scholar PubMed PubMed Central
[96] Crooke A, Basilio FH, Jesús C. The role and therapeutic potential of melatonin in age related ocular diseases. J Pineal Res. 2017;63:1–25.10.1111/jpi.12430Suche in Google Scholar PubMed
[97] Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic. Diabetes Care. 2003;26:2653–64.10.2337/diacare.26.9.2653Suche in Google Scholar PubMed
[98] Dehdashtian E, Mehrzadi S, Yousefi B, Hosseinzadeh A, Reiter RJ, Safa M, et al. Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress. Life Sci. 2018;193:20–33.10.1016/j.lfs.2017.12.001Suche in Google Scholar PubMed
[99] Santos JM, Tewari S, Kowluru RA. A compensatory mechanism protects retinal mitochondria from initial insult in diabetic retinopathy. Free Radic Biol Med. 2012;53:1729–37.10.1016/j.freeradbiomed.2012.08.588Suche in Google Scholar PubMed
[100] Djordjevic B, Cvetkovic T, Jevtovic T, Despotovic M, Zivanovic S, Basic J, et al. Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes. Eur J Pharmacol. 2018;833:290–7.10.1016/j.ejphar.2018.06.011Suche in Google Scholar PubMed
[101] Ozdemir G, Ergün Y, Bakariş S, Kılınç M, Durdu H, Ganiyusufoğlu E. Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats. Eye (Lond). 2014;28:1020–7.10.1038/eye.2014.127Suche in Google Scholar PubMed
[102] Salido EM, Zavalía N, Schreier L, De Laurentiis A, Rettori V, Chianelli M, et al. Retinal changes in an experimental model of early type 2 diabetes in rats characterized by non-fasting hyperglycemia. Exp Neurol. 2012;236:151–60.10.1016/j.expneurol.2012.04.010Suche in Google Scholar
[103] Yang JH, Kwak HW, Kim TG, Han J, Moon SW, Yu SY. Retinal neurodegeneration in type II diabetic Otsuka Long-Evans Tokushima fatty rats. IOVS 2013;54:3844–51.10.1167/iovs.12-11309Suche in Google Scholar
[104] Ellis EA, Guberski DL, Hutson B, Grant MB. Time course of NADH oxidase, inducible nitric oxide synthase and peroxynitrite in diabetic retinopathy in the BBZ/OR rat. Nitric Oxide Biol Chem. 2002;6:295–304.10.1006/niox.2001.0419Suche in Google Scholar
[105] Kumar A, Chen S, Kadiiska MB, Hong J, Zielonka J, Kalyanaraman B, et al. Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells. Free Radic Biol Med. 2014;73:51–9.10.1016/j.freeradbiomed.2014.04.014Suche in Google Scholar PubMed
[106] Al-shabrawey M, Bartoli M, El-remessy AB, Ma G, Matragoon S, Lemtalsi T, et al. Role of NADPH oxidase and Stat3 in statin-mediated protection against diabetic retinopathy. Invest Ophthalmol Vis Sci. 2008;49:3231–8.10.1167/iovs.08-1754Suche in Google Scholar PubMed
[107] Kumawat M, Kharb S, Singh V, Singh N, Singh S, Nada M. Plasma malondialdehyde (MDA) and anti-oxidant status in diabetic retinopathy. J Indian Med Assoc. 2014;112:29–32.Suche in Google Scholar PubMed
[108] Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO. Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res. 2003;22:1–29.10.1016/S1350-9462(02)00043-5Suche in Google Scholar PubMed
[109] Jiang T, Chang Q, Zhao Z, Yan S, Wang L, Cai J, et al. Melatonin-mediated cytoprotection against hyperglycemic injury in Muller cells. PLoS One 2012;7:1–8.10.1371/journal.pone.0050661Suche in Google Scholar
[110] Jiang T, Chang Q, Cai J, Fan J, Zhang X, Xu G. Protective effects of melatonin on retinal inflammation and oxidative stress in experimental diabetic retinopathy. Oxid Med Cell Longev. 2016;2016:3528274.10.1155/2016/3528274Suche in Google Scholar PubMed
[111] Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. 2009;30:1–12.10.1016/j.mam.2008.08.006Suche in Google Scholar PubMed
[112] Xie M, Hu A, Luo Y, Sun W, Hu X, Tang S. Interleukin-4 and melatonin ameliorate high glucose and interleukin-1β stimulated inflammatory reaction in human retinal endothelial cells and retinal pigment epithelial cells. Mol Vis. 2014;20:921–8.Suche in Google Scholar PubMed
[113] Salido EM, Bordone M, Laurentiis A, Chianelli M, Sarmiento MI, Dorfman D, et al. Therapeutic efficacy of melatonin in reducing retinal damage in an experimental model of early type 2 diabetes in rats. J Pineal Res. 2013;54:179–89.10.1111/jpi.12008Suche in Google Scholar
[114] Gul M, Emre S, Esrefoglu M, Vardı N. Protective effects of melatonin and aminoguanidine on the cornea in streptozotocin-induced diabetic rats. Cornea. 2008;27:795–801.10.1097/ICO.0b013e318169d67cSuche in Google Scholar PubMed
[115] Singh R, Kishore L, Kaur N. Diabetic peripheral neuropathy: current perspective and future directions. Pharmacol Res. 2014;80:21–35.10.1016/j.phrs.2013.12.005Suche in Google Scholar PubMed
[116] Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev. 2012;28:8–14.10.1002/dmrr.2239Suche in Google Scholar PubMed
[117] Tesfaye S, Vileikyte L, Rayman G, Sindrup SH, Perkins BA, Baconja M, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–38.10.1002/dmrr.1225Suche in Google Scholar PubMed
[118] Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33:2285–93.10.2337/dc10-1303Suche in Google Scholar PubMed
[119] Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012;11:521–34.10.1016/S1474-4422(12)70065-0Suche in Google Scholar PubMed
[120] Feldman EL, Nave K, Jensen TS, Bennett DL. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain. Neuron. 2017;93:1296–313.10.1016/j.neuron.2017.02.005Suche in Google Scholar PubMed
[121] Zenker J, Ziegler D, Chrast R. Novel pathogenic pathways in diabetic neuropathy. Trends Neurosci. 2013;36:439–49.10.1016/j.tins.2013.04.008Suche in Google Scholar PubMed
[122] Kuhad A, Chopra K. Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. Eur J Pharmacol. 2007;576:34–42.10.1016/j.ejphar.2007.08.001Suche in Google Scholar PubMed
[123] Jangra A, Datusalia AK, Khandwe S, Sharma SS. Amelioration of diabetes-induced neurobehavioral and neurochemical changes by melatonin and nicotinamide: implication of oxidative stress–PARP pathway. Phamarcol Biochem Behav. 2013;114–115:43–51.10.1016/j.pbb.2013.10.021Suche in Google Scholar
[124] Baydas G, Reiter RJ, Yasar A, Tuzcu M, Akdemir I, Nedzvetskii VS. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free Radic Biol Med. 2003;35:797–804.10.1016/S0891-5849(03)00408-8Suche in Google Scholar PubMed
[125] Metwally MM, Ebraheim LL, Galal AA. Potential therapeutic role of melatonin on STZ-induced diabetic central neuropathy: a biochemical, histopathological, immunohistochemical and ultrastructural study. Acta Histochem. 2018;120:828–36.10.1016/j.acthis.2018.09.008Suche in Google Scholar PubMed
[126] Leeboonngam T, Pramong R, Sae-ung K, Govitrapong P, Phansuwan-Pujito P. Neuroprotective effects of melatonin on amphetamine-induced dopaminergic fiber degeneration in the hippocampus of postnatal rats. J Pineal Res. 2018;64:1–19.10.1111/jpi.12456Suche in Google Scholar PubMed
[127] Ali T, Rehman SU, Shah FA, Kim MO. Acute dose of melatonin via Nrf2 dependently prevents acute ethanol-induced neurotoxicity in the developing rodent brain. J Neuroinflammation. 2018;15:119–38.10.1186/s12974-018-1157-xSuche in Google Scholar PubMed PubMed Central
[128] Negi G, Kumar A, Joshi RP, Sharma SS. Biochemical and biophysical research communications oxidative stress and Nrf2 in the pathophysiology of diabetic neuropathy: old perspective with a new angle. Biochem Biophys Res Commun. 2011;408:1–5.10.1016/j.bbrc.2011.03.087Suche in Google Scholar PubMed
[129] Negi G, Kumar A, Sharma SS. Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF-κB and Nrf2 cascades. J Pineal Res. 2011;50:124–31.10.1111/j.1600-079X.2010.00821.xSuche in Google Scholar PubMed
[130] Kireev RA, Cuesta S, Vara E, Tresguerres JA. Effect of growth hormone and melatonin on the brain: from molecular mechanisms to structural changes. Horm Mol Bio Clin Investig. 2011;7:337–50.10.1515/HMBCI.2011.115Suche in Google Scholar PubMed
[131] Onphachanch X, Lee HJ, Lim JR, Jung YH, Kim JS, Chae CW, et al. Enhancement of high glucose-induced PINK1 expression by melatonin stimulates neuronal cell survival: involvement of MT2/Akt/NF-κB pathway. J Pineal Res. 2017;63:1–17.10.1111/jpi.12427Suche in Google Scholar
[132] Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM. Melatonin prevents oxidative stress-induced mitochondrial dysfunction and apoptosis in high glucose-treated schwann cells via upregulation of Bcl2, NF-κB, mTOR, Wnt signalling pathways. Antioxidants (Basel). 2019;8: 1– 15.10.3390/antiox8070198Suche in Google Scholar PubMed PubMed Central
[133] Song J, Kim OY. Melatonin modulates neuronal cell death induced by endoplasmic reticulum stress under insulin resistance condition. Nutrients. 2017;9:593–608.10.3390/nu9060593Suche in Google Scholar PubMed PubMed Central
[134] Zangiabadi N, Sheibani V, Asadi-Shekaari M, Shabani M, Jafari M, Asadi AR, et al. Effects of melatonin in prevention of neuropathy in STZ-induced diabetic rats. Am J Pharmacol Toxicol. 2011;6:59–67.10.3844/ajptsp.2011.59.67Suche in Google Scholar
[135] Gokce S, Dincer M, Yaraneri H. Electrophysiological and theoretical analysis of melatonin in peripheral nerve crush injury. J Neurosci Methods. 2010;191:277–82.10.1016/j.jneumeth.2010.07.008Suche in Google Scholar PubMed
[136] Seyit DA, Degirmenci E, Oguzhanoglu A. Evaluation of electrophysiological effects of melatonin and alpha lipoic acid in rats with streptozotocine induced diabetic neuropathy. Exp Clin Endocrinol Diabetes. 2016;124:300–6.10.1055/s-0042-103750Suche in Google Scholar PubMed
[137] Chang HM, Liu CH, Hsu WM, Chen LY, Wang HP, Wu TH, et al. Proliferative effects of melatonin on Schwann cells : implication for nerve regeneration following peripheral nerve injury. J Pineal Res. 2014;56:322–32.10.1111/jpi.12125Suche in Google Scholar PubMed
© 2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Original Articles
 - The relationship between tyramine levels and inflammation in metabolic syndrome
 - Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells
 - Letter to the Editor
 - Potential implications of redefining the hypertriglyceridemia of metabolic syndrome
 - Review Article
 - A new prospective on the role of melatonin in diabetes and its complications
 
Artikel in diesem Heft
- Original Articles
 - The relationship between tyramine levels and inflammation in metabolic syndrome
 - Cholecalciferol modulates the phenotype of differentiated monocyte-derived dendritic cells without altering HIV-1 transfer to CD4+ T cells
 - Letter to the Editor
 - Potential implications of redefining the hypertriglyceridemia of metabolic syndrome
 - Review Article
 - A new prospective on the role of melatonin in diabetes and its complications