Effects of melatonin on biochemical factors and food and water consumption in diabetic rats


1 Department of Physiology, School of Medicine, North Khorasan University of Medical Sciences, Bojnourd, Iran

2 Neurocognitive Research Center and Department of Physiology, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Background: Diabetic neuropathy is one of the serious problems due to microvessel vasculopathy in diabetes. It has been reported that hyperglycemia and hypertriglyceridemia are the underlying mechanisms in inducing and progression of diabetic neuropathy. The aim of the present study was to investigate the effects of melatonin on serum glucose and lipid levels, as well as food consumption and water intake in streptozotocin-induced diabetic rats.
Materials and Methods: Eighty male Wistar rats were randomly assigned to six groups including; normal control group, diabetic control group and 4 diabetic experimental groups that received melatonin intraperitoneally at doses of 2.5, 5, 10, and 20 mg/kg at the end of sixth week after verification of neuropathy by means of evaluation of sciatic nerve conduction velocity (MNCV), for two weeks. Blood glucose and lipid levels, body weight, the amounts of food consumption, and water intake were determined in all groups at weeks 0 (before diabetes induction), 3, 6, and at the end of eighth week.
Results: Treatment with melatonin reduced significantly the serum glucose (P < 0.001) and triglyceride (P < 0.05) levels, food consumption (P < 0.001), and water intake (P < 0.001) in diabetic rats at the end of eighth week. However, melatonin had no significant effect on body weight of diabetic animals.
Conclusions: Treatment with melatonin could improve several signs of diabetes, including hyperglycemia, hypertriglyceridemia, polyphagia, and polydipsia. Therefore, melatonin may be used as an adjunct therapy in the treatment of diabetes.


1. Wada R, Yagihashi S. Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Ann N Y Acad Sci 2005;1043:598-604.  Back to cited text no. 1
2. Liu W, Liu P, Tao S, Deng Y, Li X, Lan T, et al. Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose. Arch Biochem Biophys 2008;475:128-34.  Back to cited text no. 2
3. Ghavami H, Ahmadi F, Mehin S, Meamarian R, Entezami H. Assessment of the relation between diabetic neuropathy and amp; HbA1C Concentration. Razi J Med Sci 2007;13:141-7.  Back to cited text no. 3
4. Asadi YA, Sharifi AM. Assessment of protective (antioxidant) effect of Silymarine on cell death and lipid peroxidation due to high glucose concentration in PC12 cultured cells. Iran's Diabetes Lipid Mag 2010;9:227-34.  Back to cited text no. 4
5. Obrosova IG. Diabetes and the peripheral nerve. Biochim Biophys Acta 2009;1792:931-40.  Back to cited text no. 5
6. Ghanavati TS, Goharpey S, Arastoo AA. Functional balance in diabetic neuropathy. Iran J Endocrinol Metab 2009;11:1-9.  Back to cited text no. 6
7. Davidson E, Coppey L, Lu B, Arballo V, Calcutt NA, Gerard C, et al. The roles of streptozotocin neurotoxicity and neutral endopeptidase in murine experimental diabetic neuropathy. Exp Diabetes Res 2010;2009:431980.  Back to cited text no. 7
8. Vincent AM, Hayes JM, McLean LL, Vivekanandan-Giri A, Pennathur S, Feldman EL. Dyslipidemia-induced neuropathy in mice: The role of oxLDL/LOX-1. Diabetes 2009;58:2376-85.  Back to cited text no. 8
9. Tan DX, Manchester LC, Burkhardt S, Sainz RM, Mayo JC, Kohen R, et al. N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant. FASEB J 2001;15:2294-6.  Back to cited text no. 9
10. Antolín I, Rodríguez C, Saínz RM, Mayo JC, Uría H, Kotler ML, et al. Neurohormone melatonin prevents cell damage: Effect on gene expression for antioxidant enzymes. FASEB J 1996;10:882-90.  Back to cited text no. 10
11. Montano ME, Molpeceres V, Mauriz JL, Garzo E, Cruz IB, Gonzalez P, et al. Effect of melatonin supplementation on food and water intake in streptozotocin-diabetic and non-diabetic male Wistar rats. Nutr Hosp 2010;25:931-8.  Back to cited text no. 11
12. Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food 2013;16;206-10.  Back to cited text no. 12
13. Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus. J Pineal Res 2002;32:225-30.  Back to cited text no. 13
14. Baltaci AK, Mogulkoc R. Pinealectomy and melatonin administration in rats: Their effects on plasma leptin levels and relationship with zinc. Acta Biol Hung 2007;58:335-43.  Back to cited text no. 14
15. 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.  Back to cited text no. 15
16. Negi G, Kumar A, Kaundal RK, Gulati A, Sharma SS. Functional and biochemical evidence indicating beneficial effect of Melatonin and Nicotinamide alone and in combination in experimental diabetic neuropathy. Neuropharmacology 2010;58:585-92.  Back to cited text no. 16
17. Babaei-Balderlou F, Illkhanipour M, Heidari R, Zare S, Bernousi I. Effect of melatonin on peripheral neuropathic pain in diabetic rat. Iran J Endocrinol Metab 2009;11:79-87.  Back to cited text no. 17
18. Azad N, Emanuele NV, Abraira C, Henderson WG, Colwell J, Levin SR, et al. The effects of intensive glycemic control on neuropathy in the VA Cooperative Study on Type II Diabetes Mellitus (VA CSDM). J Diabetes Complications 1999;13:307-13.  Back to cited text no. 18
19. Wiggin TD, Sullivan KA, Pop-Busui R, Amato A, Sima AA, Feldman EL. Elevated triglycerides correlate with progression of diabetic neuropathy. Diabetes 2009;58:1634-40.  Back to cited text no. 19
20. Morel DW, Chisolm GM. Antioxidant treatment of diabetic rats inhibits lipoprotein oxidation and cytotoxicity. J Lipid Res 1989;30:1827-34.  Back to cited text no. 20
21. Anwar MM, Meki AR. Oxidative stress in streptozotocin-induced diabetic rats: Effects of garlic oil and melatonin. Comp Biochem Physiol Part A Mol Integr Physiol 2003;135:539-47.  Back to cited text no. 21
22. 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.  Back to cited text no. 22
23. Montilla PL, Vargas JF, Tunez IF, Munoz de Agueda MC, Valdelvira ME, Cabrera ES. Oxidative stress in diabetic rats induced by streptozotocin: Protective effects of melatonin. J Pineal Res 1998;25:94-100.  Back to cited text no. 23
24. 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.  Back to cited text no. 24
25. Bizot-Espiard JG, Double A, Cousin B, Lesieur D, Guardiola-Lemaitre B, Delagrange P, et al. Lack of melatonin effects on insulin action in normal rats. Hormone Metab Res 1998;30:711-6.  Back to cited text no. 25
26. 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.  Back to cited text no. 26
27. Yegin ZA, Mutluay R, Elberg S, Karakus R, Cakir N. . The impact of melatonin on glucose homeostasis. Turk J Endocrinol Metab 2009.  Back to cited text no. 27
28. 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.  Back to cited text no. 28
29. Zhang K, Lv Z, Jia X, Huang D. Melatonin prevents testicular damage in hyperlipidaemic mice. Andrologia 2012;44:230-6.  Back to cited text no. 29
30. Hoyos M, Guerrero JM, Perez-Cano R, Olivan J, Fabiani F, Garcia-Pergañeda A, et al. Serum cholesterol and lipid peroxidation are decreased by melatonin in diet-induced hypercholesterolemic rats. J Pineal Res 2000;28:150-5.  Back to cited text no. 30
31. Şener G, Balkan J, Çevikbaş U, Keyer-Uysal M, Uysal M. Melatonin reduces cholesterol accumulation and prooxidant state induced by high cholesterol diet in the plasma, the liver and probably in the aorta of C57BL/6J mice. J Pineal Res 2004;36:212-6.  Back to cited text no. 31
32. Sauer LA, Dauchy RT, Blask DE. Melatonin inhibits fatty acid transport in inguinal fat pads of hepatoma 7288CTC-bearing and normal Buffalo rats via receptor-mediated signal transduction. Life Sci 2001;68:2835-44.  Back to cited text no. 32
33. Sanchez-Hidalgo M, Lu Z, Tan DX, Maldonado MD, Reiter RJ, Gregerman RI. Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells: Implications for osteoblast differentiation and osteoporosis. Am J Physiol Regul Integr Comp Physiol 2007;292:R2208-15.  Back to cited text no. 33
34. Costa A, Bescos M, Velho G, Chevre J, Vidal J, Sesmilo G, et al. Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families. Eur J Endocrinol 2000;142:380-6.  Back to cited text no. 34
35. 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.  Back to cited text no. 35
36. Srinivasan V, Ohta Y, Espino J, Pariente JA, Rodriguez AB, Mohamed M, et al. Metabolic syndrome, its pathophysiology and the role of melatonin. Recent Pat Endocr Metab Immune Drug Discov 2013;7:11-25.  Back to cited text no. 36
37. 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.  Back to cited text no. 37
38. Prunet-Marcassus B, Ambid L, Viguerie-Bascands N, Pénicaud L, Casteilla L. Evidence for a direct effect of melatonin on mitochondrial genome expression of Siberian hamster brown adipocytes. J Pineal Res 2001;30:108-15.  Back to cited text no. 38
39. Youngstrom TG, Bartness TJ. Catecholaminergic innervation of white adipose tissue in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol 1995;268:R744-51.  Back to cited text no. 39