Melatonin and Type 2 Diabetes Mellitus: the Role of Melatonin on Pathophysiology of the Disease and Potential Therapeutic

Authors

  • Ni Putu Dian Prakanita Dewi Faculty of Medicine, Universitas Tarumanagara
  • Nadila Nadila Faculty of Medicine, Universitas Tarumanagara
  • Nadila Nadila Faculty of Medicine, Universitas Tarumanagara
  • Andreas Galih Sidharta Sugiarto Faculty of Medicine, Universitas Tarumanagara
  • Kelnia Mellenia Faculty of Medicine, Universitas Tarumanagara
  • Ade Anjalita Santi Dewi Faculty of Medicine, Universitas Tarumanagara

DOI:

https://doi.org/10.32583/keperawatan.v14i4.1503

Keywords:

melatonin, pathophysiology, therapeutic potential, type 2 diabetes mellitus

Abstract

Diabetes is a global health problem, with the latest data showing a global prevalence of 536,6 million (10,5%) people. The risk factors involved in the pathogenesis of diabetes, especially Type 2 Diabetes Mellitus (T2DM), are also varied, including a combination of risk factors such as age, obesity, sedentary lifestyle, environmental factors, and genetics. On the other hand, the complications associated with T2DM are also quite diverse, including diabetic neuropathy, retinopathy, nephropathy, and cardiovascular disease. Several theories have been proposed to explain the pathogenesis of complications in T2DM, one of which is cell damage due to oxidative stress. Melatonin is a hormone produced by the pineal gland known for its antioxidant properties, which can provide various therapeutic effects and health benefits, including in T2DM patients.  Objective to explain further the bioactivity of melatonin, food sources of melatonin, and the role of melatonin in the pathophysiology of diseases related to its therapeutic potential in individuals with T2DM. This literature review selected various related scientific studies published within the last 10 (ten) years. A literature search was conducted through databases, such as PubMed and Science Direct, with the keywords "melatonin", "Type 2 Diabetes Mellitus", "pathophysiology", and "therapeutic potential". Hyperglycemia in T2DM leads to excessive ROS production, which then causes oxidative stress accumulation and insulin resistance induction. Oxidative stress is known to be associated with many other complications of diabetes, such as cardiomyopathy, retinopathy, and diabetic neuropathy. Melatonin has been shown to protect diabetes through various mechanisms, such as increasing antioxidant status, inhibiting the apoptotic pathway, suppressing inflammation, and acting as a neuroprotective agent. Melatonin supplementation can be used as a therapeutic step to improve pathological conditions in patients and reduce the incidence of T2DM complications.

References

Acuña-Castroviejo, D., Escames, G., Venegas, C., Díaz-Casado, M. E., Lima-Cabello, E., López, L. C., Rosales-Corral, S., Tan, D. X., & Reiter, R. J. (2014). Extrapineal melatonin: Sources, regulation, and potential functions. Cellular and Molecular Life Sciences, 71(16), 2997–3025. https://doi.org/10.1007/s00018-014-1579-2

Agil, A., El-Hammadi, M., Jiménez-Aranda, A., Tassi, M., Abdo, W., Fernández-Vázquez, G., & Reiter, R. J. (2015). Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats. Journal of Pineal Research, 59(1), 70–79. https://doi.org/10.1111/jpi.12241

Agil, A., Elmahallawy, E. K., Rodríguez-Ferrer, J. M., Adem, A., Bastaki, S. M., Al-Abbadi, I., Fino Solano, Y. A., & Navarro-Alarcón, M. (2015). Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats. Food and Function, 6(8), 2671–2678. https://doi.org/10.1039/c5fo00590f

Aguilera, Y., Herrera, T., Liébana, R., Rebollo-Hernanz, M., Sanchez-Puelles, C., & Martín-Cabrejas, M. A. (2015). Impact of Melatonin Enrichment during Germination of Legumes on Bioactive Compounds and Antioxidant Activity. Journal of Agricultural and Food Chemistry, 63(36), 7967–7974. https://doi.org/10.1021/acs.jafc.5b03128

Ali, T., Rehman, S. U., Shah, F. A., & Kim, M. O. (2018). Acute dose of melatonin via Nrf2 dependently prevents acute ethanol-induced neurotoxicity in the developing rodent brain. Journal of Neuroinflammation, 15(1). https://doi.org/10.1186/s12974-018-1157-x

Amaral, F. G., Turati, A. O., Barone, M., Scialfa, J. H., Do Carmo Buonfiglio, D., Peres, R., Peliciari-Garcia, R. A., Afeche, S. C., Lima, L., Scavone, C., Bordin, S., Reiter, R. J., Menna-Barreto, L., & Cipolla-Neto, J. (2014). Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia. Journal of Pineal Research, 57(1), 67–79. https://doi.org/10.1111/jpi.12144

Amin, A. H., El-Missiry, M. A., & Othman, A. I. (2015). Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis. European Journal of Pharmacology, 747, 166–173. https://doi.org/10.1016/j.ejphar.2014.12.002

Aranda-Rivera, A. K., Cruz-Gregorio, A., Arancibia-Hernández, Y. L., Hernández-Cruz, E. Y., & Pedraza-Chaverri, J. (2022). RONS and Oxidative Stress: An Overview of Basic Concepts. Oxygen, 2(4), 437–478. https://doi.org/10.3390/oxygen2040030

Barton, S. K., Tolcos, M., Miller, S. L., Roehr, C. C., Schmölzer, G. M., Moss, T. J. M., Hooper, S. B., Wallace, E. M., & Polglase, G. R. (2016). Ventilation-Induced Brain Injury in Preterm Neonates: A Review of Potential Therapies. Neonatology, 110(2), 155–162. https://doi.org/10.1159/000444918

Bielli, A., Scioli, M. G., Mazzaglia, D., Doldo, E., & Orlandi, A. (2015). Antioxidants and vascular health. Life Sciences, 143, 209–216. https://doi.org/10.1016/j.lfs.2015.11.012

Bondeva, T., & Wolf, G. (2014). Reactive oxygen species in diabetic nephropathy: Friend or foe? Nephrology Dialysis Transplantation, 29(11), 1998–2003. https://doi.org/10.1093/ndt/gfu037

Borghetti, G., Von Lewinski, D., Eaton, D. M., Sourij, H., Houser, S. R., & Wallner, M. (2018). Diabetic cardiomyopathy: Current and future therapies. Beyond glycemic control. Frontiers in Physiology, 9(OCT). https://doi.org/10.3389/fphys.2018.01514

Bosco, A. D., Schedler, F. B., Colares, J. R., Schemitt, E. G., Hartmann, R. M., Forgiarini Junior, L. A., Dias, A. S., & Marroni, N. P. (2019). Melatonin effects on pulmonary tissue in the experimental model of hepatopulmonary syndrome. Jornal Brasileiro de Pneumologia, 45(3). https://doi.org/10.1590/1806-3713/e20170164

Chang, H. M., Liu, C. H., Hsu, W. M., Chen, L. Y., Wang, H. P., Wu, T. H., Chen, K. Y., Ho, W. H., & Liao, W. C. (2014). Proliferative effects of melatonin on Schwann cells: Implication for nerve regeneration following peripheral nerve injury. Journal of Pineal Research, 56(3), 322–332. https://doi.org/10.1111/jpi.12125

Chawla, D., & Kumar Tripathi, A. (2019). Role of advanced glycation end products (AGEs) and its receptor (RAGE)-mediated diabetic vascular complications. Integrative Food, Nutrition and Metabolism, 6(5). https://doi.org/10.15761/ifnm.1000267

Chen, H. H., Lin, K. C., Wallace, C. G., Chen, Y. T., Yang, C. C., Leu, S., Chen, Y. C., Sun, C. K., Tsai, T. H., Chen, Y. L., Chung, S. Y., Chang, C. Lo, & Yip, H. K. (2014). Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury. Journal of Pineal Research, 57(1), 16–32. https://doi.org/10.1111/jpi.12140

Chen, S. J., Huang, S. H., Chen, J. W., Wang, K. C., Yang, Y. R., Liu, P. F., Lin, G. J., & Sytwu, H. K. (2016). Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis. International Immunopharmacology, 31, 169–177. https://doi.org/10.1016/j.intimp.2015.12.020

Costello, R. B., Lentino, C. V., Boyd, C. C., O’Connell, M. L., Crawford, C. C., Sprengel, M. L., & Deuster, P. A. (2014). The effectiveness of melatonin for promoting healthy sleep: A rapid evidence assessment of the literature. Nutrition Journal, 13(1). https://doi.org/10.1186/1475-2891-13-106

Crooke, A., Huete-Toral, F., Colligris, B., & Pintor, J. (2017). The role and therapeutic potential of melatonin in age-related ocular diseases. Journal of Pineal Research, 63(2). https://doi.org/10.1111/jpi.12430

Dehdashtian, E., Mehrzadi, S., Yousefi, B., Hosseinzadeh, A., Reiter, R. J., Safa, M., Ghaznavi, H., & Naseripour, M. (2018). Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress. Life Sciences, 193, 20–33. https://doi.org/10.1016/j.lfs.2017.12.001

Djordjevic, B., Cvetkovic, T., Stoimenov, T. J., Despotovic, M., Zivanovic, S., Basic, J., Veljkovic, A., Velickov, A., Kocic, G., Pavlovic, D., & Sokolovic, D. (2018). 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. European Journal of Pharmacology, 833, 290–297. https://doi.org/10.1016/j.ejphar.2018.06.011

Feldman, E. L., Nave, K. A., Jensen, T. S., & Bennett, D. L. H. (2017). New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain. Neuron, 93(6), 1296–1313. https://doi.org/10.1016/j.neuron.2017.02.005

Fonken, L. K., & Nelson, R. J. (2014). The effects of light at night on circadian clocks and metabolism. Endocrine Reviews, 35(4), 648–670. https://doi.org/10.1210/er.2013-1051

Greenhill, C. (2016). Risk Factors: Melatonin signalling implicated in the risk of T2DM. Nature Reviews Endocrinology, 12(7), 374. https://doi.org/10.1038/nrendo.2016.85

Gregg, E. W., Li, Y., Wang, J., Rios Burrows, N., Ali, M. K., Rolka, D., Williams, D. E., & Geiss, L. (2014). Changes in Diabetes-Related Complications in the United States, 1990–2010. New England Journal of Medicine, 370(16), 1514–1523. https://doi.org/10.1056/nejmoa1310799

Hernández-Plata, E., Quiroz-Compeán, F., Ramírez-Garcia, G., Barrientos, E. Y., Rodríguez-Morales, N. M., Flores, A., Wrobel, K., Wrobel, K., Méndez, I., Díaz-Muñoz, M., Robles, J., & Martínez-Alfaro, M. (2015). Melatonin reduces lead levels in blood, brain and bone and increases lead excretion in rats subjected to subacute lead treatment. Toxicology Letters, 233(2), 78–83. https://doi.org/10.1016/j.toxlet.2015.01.009

Jameson, J. L., Kasper, D. L., Longo, D. L., Fauci, A. S., Hauser, S. L., & Loscalzo, J. (2020). Harrison’s Principles of Internal Medicine, Twentieth Edition. McGraw-Hill Education.

Jia, G., Hill, M. A., & Sowers, J. R. (2018). Diabetic cardiomyopathy: An update of mechanisms contributing to this clinical entity. Circulation Research, 122(4), 624–638. https://doi.org/10.1161/CIRCRESAHA.117.311586

Jin, Q., & Ma, R. C. W. (2021). Metabolomics in diabetes and diabetic complications: Insights from epidemiological studies. Cells, 10(11). https://doi.org/10.3390/cells10112832

Karabulut-Bulan, O., Bayrak, B. B., Arda-Pirincci, P., Sarikaya-Unal, G., Us, H., & Yanardag, R. (2015). Role of Exogenous Melatonin on Cell Proliferation and Oxidant/Antioxidant System in Aluminum-Induced Renal Toxicity. Biological Trace Element Research, 168(1), 141–149. https://doi.org/10.1007/s12011-015-0320-9

Karunanithi, D., Radhakrishna, A., Sivaraman, K. P., & Biju, V. M. N. (2014). Quantitative determination of melatonin in milk by LC-MS/MS. Journal of Food Science and Technology, 51(4), 805–812. https://doi.org/10.1007/s13197-013-1221-6

Kumar, A., Chen, S. H., Kadiiska, M. B., Hong, J. S., Zielonka, J., Kalyanaraman, B., & Mason, R. P. (2014). Inducible nitric oxide synthase is key to peroxynitrite-mediated, LPS-induced protein radical formation in murine microglial BV2 cells. Free Radical Biology and Medicine, 73, 51–59. https://doi.org/10.1016/j.freeradbiomed.2014.04.014

Kumawat, M., Kharb, S., Singh, V., Singh, N., Singh, S. K., & Nada, M. (2014). Plasma malondialdehyde (MDA) and anti-oxidant status in diabetic retinopathy. Journal of the Indian Medical Association, 112(1), 29–32.

Leeboonngam, T., Pramong, R., Sae-ung, K., Govitrapong, P., & Phansuwan-Pujito, P. (2018). Neuroprotective effects of melatonin on amphetamine-induced dopaminergic fiber degeneration in the hippocampus of postnatal rats. Journal of Pineal Research, 64(3). https://doi.org/10.1111/jpi.12456

Li, A. N., Li, S., Zhang, Y. J., Xu, X. R., Chen, Y. M., & Li, H. Bin. (2014). Resources and biological activities of natural polyphenols. Nutrients, 6(12), 6020–6047. https://doi.org/10.3390/nu6126020

Li, M., Pi, H., Yang, Z., Reiter, R. J., Xu, S., Chen, X., Chen, C., Zhang, L., Yang, M., Li, Y., Guo, P., Li, G., Tu, M., Tian, L., Xie, J., He, M., Lu, Y., Zhong, M., Zhang, Y., … Zhou, Z. (2016). Melatonin antagonizes cadmium-induced neurotoxicity by activating the transcription factor EB-dependent autophagy–lysosome machinery in mouse neuroblastoma cells. Journal of Pineal Research, 353–369. https://doi.org/10.1111/jpi.12353

Lo, C. C., Lin, S. H., Chang, J. S., & Chien, Y. W. (2017). Effects of melatonin on glucose homeostasis, antioxidant ability, and adipokine secretion in ICR mice with NA/STZ-induced hyperglycemia. Nutrients, 9(11). https://doi.org/10.3390/nu9111187

Meng, X., Li, Y., Li, S., Zhou, Y., Gan, R. Y., Xu, D. P., & Li, H. Bin. (2017). Dietary sources and bioactivities of melatonin. Nutrients, 9(4). https://doi.org/10.3390/nu9040367

Metwally, M. M. M., Ebraheim, L. L. M., & Galal, A. A. A. (2018). Potential therapeutic role of melatonin on STZ-induced diabetic central neuropathy: A biochemical, histopathological, immunohistochemical and ultrastructural study. Acta Histochemica, 120(8), 828–836. https://doi.org/10.1016/j.acthis.2018.09.008

Milagres, M. P., Minim, V. P. R., Minim, L. A., Simiqueli, A. A., Moraes, L. E. S., & Martino, H. S. D. (2014). Night milking adds value to cow’s milk. Journal of the Science of Food and Agriculture, 94(8), 1688–1692. https://doi.org/10.1002/jsfa.6480

Mok, J. X., Ooi, J. H., Ng, K. Y., Koh, R. Y., & Chye, S. M. (2019). A new prospective on the role of melatonin in diabetes and its complications. Hormone Molecular Biology and Clinical Investigation. https://doi.org/10.1515/hmbci-2019-0036

Mulder, H. (2017). Melatonin signalling and type 2 diabetes risk: too little, too much or just right? Diabetologia, 60(5), 826–829. https://doi.org/10.1007/s00125-017-4249-8

Navarro-Alarcon, M., Ruiz-Ojeda, F. J., Blanca-Herrera, R. M., Kaki, A., Adem, A., & Agil, A. (2014). Melatonin administration in diabetes: Regulation of plasma Cr, V, and Mg in young male Zucker diabetic fatty rats. Food and Function, 5(3), 512–516. https://doi.org/10.1039/c3fo60389j

NaveenKumar, S. K., Hemshekhar, M., Kemparaju, K., & Girish, K. S. (2019). Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: Protection by Melatonin. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1865(9), 2303–2316. https://doi.org/10.1016/j.bbadis.2019.05.009

Oladi, E., Mohamadi, M., Shamspur, T., & Mostafavi, A. (2014). Spectrofluorimetric determination of melatonin in kernels of four different Pistacia varieties after ultrasound-assisted solid-liquid extraction. Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 132, 326–329. https://doi.org/10.1016/j.saa.2014.05.010

Oliveira, A. C. de, Andreotti, S., Sertie, R. A. L., Campana, A. B., de Proença, A. R. G., Vasconcelos, R. P., Oliveira, K. A. de, Coelho-de-Souza, A. N., Donato-Junior, J., & Lima, F. B. (2018). Combined treatment with melatonin and insulin improves glycemic control, white adipose tissue metabolism and reproductive axis of diabetic male rats. Life Sciences, 199, 158–166. https://doi.org/10.1016/j.lfs.2018.02.040

Onphachanh, X., Lee, H. J., Lim, J. R., Jung, Y. H., Kim, J. S., Chae, C. W., Lee, S. J., Gabr, A. A., & Han, H. J. (2017). Enhancement of high glucose-induced PINK1 expression by melatonin stimulates neuronal cell survival: Involvement of MT2/Akt/NF-κB pathway. Journal of Pineal Research, 63(2). https://doi.org/10.1111/jpi.12427

Özdemir, G., Ergün, Y., Bakariş, S., Kilinç, M., Durdu, H., & Ganiyusufoʇlu, E. (2014). Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats. Eye (Basingstoke), 28(8), 1020–1027. https://doi.org/10.1038/eye.2014.127

Paredes, S. D., Forman, K. A., García, C., Vara, E., Escames, G., & Tresguerres, J. A. F. (2014). Protective actions of melatonin and growth hormone on the aged cardiovascular system. Hormone Molecular Biology and Clinical Investigation, 18(2), 79–88. https://doi.org/10.1515/hmbci-2014-0016

Pourhanifeh, M. H., Hosseinzadeh, A., Dehdashtian, E., Hemati, K., & Mehrzadi, S. (2020). Melatonin: New insights on its therapeutic properties in diabetic complications. Diabetology and Metabolic Syndrome, 12(1). https://doi.org/10.1186/s13098-020-00537-z

Prasad, R. B., & Groop, L. (2015). Genetics of type 2 diabetes—pitfalls and possibilities. Genes, 6(1), 87–123. https://doi.org/10.3390/genes6010087

Reiter, R. J., Mayo, J. C., Tan, D. X., Sainz, R. M., Alatorre-Jimenez, M., & Qin, L. (2016). Melatonin as an antioxidant: under promises but over delivers. Journal of Pineal Research, 253–278. https://doi.org/10.1111/jpi.12360

Reiter, R. J., Tan, D. X., Rosales-Corral, S., Galano, A., Zhou, X. J., & Xu, B. (2018). Mitochondria: Central organelles for melatonins antioxidant and anti-Aging actions. Molecules, 23(2). https://doi.org/10.3390/molecules23020509

Rybka, J., Kędziora-Kornatowska, K., Kupczyk, D., Muszalik, M., Kornatowski, M., & Kędziora, J. (2016). Antioxidant effect of immediate-versus sustained-release melatonin in type 2 diabetes mellitus and healthy controls. Drug Delivery, 23(3), 814–817. https://doi.org/10.3109/10717544.2014.917343

Rzepka-Migut, B., & Paprocka, J. (2020). Melatonin-Measurement Methods and the Factors Modifying the Results. A Systematic Review of the Literature. International Journal of Environmental Research and Public Health, 17(6), 1916. https://doi.org/10.3390/ijerph17061916

Salehi, B., Sharopov, F., Fokou, P. V. T., Kobylinska, A., de Jonge, L., Tadio, K., Sharifi-Rad, J., Posmyk, M. M., Martorell, M., Martins, N., & Iriti, M. (2019). Melatonin in medicinal and food plants: Occurrence, bioavailability, and health potential for humans. Cells, 8(7). https://doi.org/10.3390/cells8070681

Setyaningsih, W., Saputro, I. E., Barbero, G. F., Palma, M., & García Barroso, C. (2015). Determination of melatonin in rice (Oryza sativa) grains by pressurized liquid extraction. Journal of Agricultural and Food Chemistry, 63(4), 1107–1115. https://doi.org/10.1021/jf505106m

Seyit, D. A., Degirmenci, E., & Oguzhanoglu, A. (2016). Evaluation of Electrophysiological Effects of Melatonin and Alpha Lipoic Acid in Rats with Streptozotocine Induced Diabetic Neuropathy. Experimental and Clinical Endocrinology and Diabetes, 124(5), 300–306. https://doi.org/10.1055/s-0042-103750

Shah, N., Abdalla, M. A., Deshmukh, H., & Sathyapalan, T. (2021). Therapeutics for type-2 diabetes mellitus: a glance at the recent inclusions and novel agents under development for use in clinical practice. Therapeutic Advances in Endocrinology and Metabolism, 12. https://doi.org/10.1177/20420188211042145

She, M., Laudon, M., & Yin, W. (2015). Melatonin receptors in diabetes: A potential new therapeutical target? European Journal of Pharmacology, 744, 220–223. https://doi.org/10.1016/j.ejphar.2014.08.012

Singh, A. K., & Haldar, C. (2014). Age dependent nitro-oxidative load and melatonin receptor expression in the spleen and immunity of goat Capra hircus. Experimental Gerontology, 60, 72–78. https://doi.org/10.1016/j.exger.2014.09.017

Singh, M., & Jadhav, H. R. (2014). Melatonin: Functions and ligands. Drug Discovery Today, 19(9), 1410–1418. https://doi.org/10.1016/j.drudis.2014.04.014

Singh, R., Kishore, L., & Kaur, N. (2014). Diabetic peripheral neuropathy: Current perspective and future directions. Pharmacological Research, 80, 21–35. https://doi.org/10.1016/j.phrs.2013.12.005

Song, J., & Kim, O. Y. (2017). Melatonin modulates neuronal cell death induced by endoplasmic reticulum stress under insulin resistance condition. Nutrients, 9(6). https://doi.org/10.3390/nu9060593

Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Stein, C., Basit, A., Chan, J. C. N., Mbanya, J. C., Pavkov, M. E., Ramachandaran, A., Wild, S. H., James, S., Herman, W. H., Zhang, P., Bommer, C., Kuo, S., Boyko, E. J., & Magliano, D. J. (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183. https://doi.org/10.1016/j.diabres.2021.109119

Tan, D. X., Manchester, L. C., Esteban-Zubero, E., Zhou, Z., & Reiter, R. J. (2015). Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism. Molecules, 20(10), 18886–18906. https://doi.org/10.3390/molecules201018886

Tan, D. X., Zanghi, B. M., Manchester, L. C., & Reiter, R. J. (2014). Melatonin identified in meats and other food stuffs: Potentially nutritional impact. Journal of Pineal Research, 57(2), 213–218. https://doi.org/10.1111/jpi.12152

Tiong, Y. L., Ng, K. Y., Koh, R. Y., Ponnudurai, G., & Chye, S. M. (2019). 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, 8(7). https://doi.org/10.3390/antiox8070198

Tuomi, T., Nagorny, C. L. F., Singh, P., Bennet, H., Yu, Q., Alenkvist, I., Isomaa, B., Östman, B., Söderström, J., Pesonen, A. K., Martikainen, S., Räikkönen, K., Forsén, T., Hakaste, L., Almgren, P., Storm, P., Asplund, O., Shcherbina, L., Fex, M., … Mulder, H. (2016). Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes. Cell Metabolism, 23(6), 1067–1077. https://doi.org/10.1016/j.cmet.2016.04.009

Wang, C., Yin, L. Y., Shi, X. Y., Xiao, H., Kang, K., Liu, X. Y., Zhan, J. C., & Huang, W. D. (2016). Effect of Cultivar, Temperature, and Environmental Conditions on the Dynamic Change of Melatonin in Mulberry Fruit Development and Wine Fermentation. Journal of Food Science, 81(4), M958–M967. https://doi.org/10.1111/1750-3841.13263

Wang, J., & Wang, H. (2017). Oxidative stress in pancreatic beta cell regeneration. Oxidative Medicine and Cellular Longevity, 2017. https://doi.org/10.1155/2017/1930261

Wu, Y., Ding, Y., Tanaka, Y., & Zhang, W. (2014). Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention. International Journal of Medical Sciences, 11(11), 1185–1200. https://doi.org/10.7150/ijms.10001

Yu, L., Gong, B., Duan, W., Fan, C., Zhang, J., Li, Z., Xue, X., Xu, Y., Meng, D., Li, B., Zhang, M., Zhang, B., Jin, Z., Yu, S., Yang, Y., & Wang, H. (2017). Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: Role of AMPK-PGC-1α-SIRT3 signaling. Scientific Reports, 7. https://doi.org/10.1038/srep41337

Zephy, D., & Ahmad, J. (2015). Type 2 diabetes mellitus: Role of melatonin and oxidative stress. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 9(2), 127–131. https://doi.org/10.1016/j.dsx.2014.09.018

Zhang, Y. J., Gan, R. Y., Li, S., Zhou, Y., Li, A. N., Xu, D. P., Li, H. Bin, & Kitts, D. D. (2015). Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules, 20(12), 21138–21156. https://doi.org/10.3390/molecules201219753

Zhang, Y., Wei, Z., Liu, W., Wang, J., He, X., Huang, H., Zhang, J., & Yang, Z. (2017). Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway. Oncotarget, 8(3), 3773–3780. https://doi.org/10.18632/oncotarget.13931

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12/28/2022

How to Cite

Dewi, N. P. D. P. ., Nadila, N., Nadila, N., Sugiarto, A. G. S., Mellenia, K. ., & Dewi, A. A. S. . (2022). Melatonin and Type 2 Diabetes Mellitus: the Role of Melatonin on Pathophysiology of the Disease and Potential Therapeutic. Jurnal Keperawatan, 14(4), 1165–1180. https://doi.org/10.32583/keperawatan.v14i4.1503