Keywords
Serotonina
Receptores de serotonina
Serotoninérgicos
Diabetes mellitus
Farmacología Tryptophan
Serotonin
Receptors
Serotonin agents
Diabetes mellitus
Pharmacology
How to Cite
Abstract
Non-systematic literature review that focuses on the roles of serotoninergic system in diabetes mellitus pathophysiology and its related pharmacological targets. It is described the biochemistry and physiology of 5-hidroxitriptamine (5HT), as well as its carrier, 5HT receptors families and subtypes in regulatory actions of carbohydrates metabolism, insulin and glucagon secretion, and appetite control in coactivation with leptin. Were included studies related to serotonin role in carcinoid syndrome and diabetes vascular complications, and studies about measurement of metabolites (5-hidroxindolacetic acid and xanturenic acid) as potential biomarkers of diabetes. Finally, it is introduced the evidence of the hipoglicemiant effect of three groups of serotonin metabolism regulatory medicines: selective serotonin reuptake inhibitors, 5HT-receptors agonists and antagonists, and 5-tryptophan-hidroxilase (Tph) enzymes antagonists.
References
Wade JM, Juneja P, MacKay AW, Graham J, Havel PJ, Tecott LH, et al. Synergistic Impairment of Glucose Homeostasis in ob/ob Mice Lacking Functional Serotonin 2C Receptors. Endocrinology. 2008 Mar; 149(3): 955-61. https://doi.org/10.1210/en.2007-0927
Prabhakar V, Gupta D, Kanade P, Radhakrishnan M. Diabetes-associated depression: The serotonergic system as a novel multifunctional target. Indian J Pharmacol. 2015 Jan-Feb; 47(1): 4-10. https://doi.org/10.4103/0253-7613.150305
Knol MJ, Derijks HJ, Geerlings MI, Heerdink ER, Souverein PC, Gorter KJ, et al. Influence of antidepressants on glycaemic control in patients with diabetes mellitus. Pharmacoepidemiology and drug safety. 2008; 17: 577-58. https://doi.org/10.1002/pds.1608
Ohta Y, Kosaka Y, Kishimoto N, Wang J, Smith SB, Honig G, et al. Convergence of the Insulin and Serotonin Programs in the Pancreatic-Cell. Diabetes. 2011 Dec; 60(12): 3208-16 https://doi.org/10.2337/db10-1192
Chang-Myung O, Sangkyu P, Hail K. Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity. Diabetes Metab J. 2016; 40: 89-98. https://doi.org/10.4093/dmj.2016.40.2.89
Robinson R. Serotonin's Role in the Pancreas Revealed at Last. PLoS Biology. 2009; 7(10):e1000227. https://doi.org/10.1371/journal.pbio.1000227
Oka M, Leppänen VVE. Metabolism of Tryptophan in Diabetes Mellitus. Acta Medica Scandinavica. 1963; 173, fasc. 3. 361-64. https://doi.org/10.1111/j.0954-6820.1963.tb17417.x
Manjarrez G, Herrera-Márquez JR, Bueno-Santoyo S, González-Ramírez M, Hernández-Rodríguez J. Cambios en la biosíntesis de serotonina cerebral en ratas con diabetes mellitus inducida por estreptozotocina. Revista de Investigación Clínica. 2000; 52(5): 509-15.
Chen T, Zheng X, Ma X, Bao Y, Ni Y, Hu C, et al. Tryptophan Predicts the Risk for Future Type 2 Diabetes. PLoS ONE. 2016, 11(9): e0162192. https://doi.org/10.1371/journal.pone.0162192
Watanabe H, Rose MT, Aso H. Role of peripheral serotonin in glucose and lipid metabolism. Current Opinion in Lipidology. 2011, 22: 186-191. https://doi.org/10.1097/MOL.0b013e3283462273
Shpakov AO, Derkach KV, Berstein LM. Brain signaling systems in the Type 2 diabetes and metabolic syndrome: promising target to treat and prevent these diseases. Future Sci. OA. 2015, 1(3), FSO25. https://doi.org/10.4155/fso.15.23
Yang Y, Huang H, Xu Z, Duan JK. Serotonin and Its Receptor as a New Antioxidant Therapeutic Target for Diabetic Kidney Disease. Journal of Diabetes Research, 2017. ID7680576. https://doi.org/10.1155/2017/7680576
Cataldo LR, Cortés VA, Galgani JE, Olmos PR, Santos JL. Papel de la serotonina periférica en la secreción de insulina y la homeostasis de la glucosa. Nutr Hosp. 2014; 30: 498-508.
Almaça J, Molina J, Menegaz D, Slepak V, Berggren PO, Caicedo A. Human Beta Cells Produce and Release Serotonin to Inhibit Glucagon Secretion from Alpha Cells. Cell Reports. 2016, 17, 3281-91. https://doi.org/10.1016/j.celrep.2016.11.072
Zhou L, Sutton GM, Rochford JJ, Semple RK, Lam DD, Oksanen LJ, et al. Serotonin 2C Receptor Agonists Improve Type 2 Diabetes via Melanocortin-4 Receptor Signaling Pathways. Cell Metab. 2007 Nov; 6(5): 398-405. https://doi.org/10.1016/j.cmet.2007.10.008
Chen H, Hong F, Chen Y, Li J, Yao YS, Zhang Y, et al. Activation of islet 5-HT4 receptor regulates glycemic control through promoting insulin secretion. European Journal of Pharmacology, 2016. 789: 354-61. https://doi.org/10.1016/j.ejphar.2016.07.024
Bennet H, Balhuizen A, Medina A, Dekker-Nitert M, Ottosson-Laakso A, S. Essén S, et al. Altered serotonin (5-HT) 1D and 2A receptor expression may contribute to defective insulin and glucagon secretion in human type 2 diabetes. Peptides, 2015. 71: 113-120. https://doi.org/10.1016/j.peptides.2015.07.008
Kim K, Oh CM, Ohara-Imaizumi M, Park S, Namkung J, Yadav VK, et al. Functional Role of Serotonin in Insulin Secretion in a Diet-Induced InsulinResistant State. Endocrinology. 2015 Feb; 156(2): 444-452. https://doi.org/10.1210/en.2014-1687
Smith BK, York DA, Bray GA. Activation of hypothalamic serotonin receptors reduce intake of dietary fat and protein but not carbohydrate. Am J Physiol. 1999 Sep; 277(3 Pt 2): R802-11. https://doi.org/10.1152/ajpregu.1999.277.3.R802