¿Los protocolos experimentales son un símil real de la diabetes humana?
DOI:
https://doi.org/10.29059/cienciauat.v14i2.1289Palabras clave:
modelos experimentales, diabetes, aloxana, estreptozotocina, hiperglucemiaResumen
Para el estudio de la diabetes se dispone de diversas estrategias metodológicas en modelos animales, tales como, técnicas quirúrgicas, modificaciones dietéticas, incluso manipulación genética y la administración de fármacos específicos, por su toxicidad. En animales, la diabetes experimental se logra con el uso de fármacos, como la aloxana o la estreptozotocina, los cuales producen daño irreversible en las células-pancreáticas, aunque causan una alta mortalidad, debido a la cetosis asociada al daño agudo de estas células pancreáticas. El objetivo de este trabajo fue analizar los protocolos farmacológicos y otras estrategias disponibles, para determinar si la diabetes experimental realmente emula la diabetes humana. La diabetes es un proceso progresivo y crónico, en el que la mayor parte de las alteraciones clínicas son consecuencia, en el largo plazo, de alteraciones micro y macrovasculares. Por ello, es conveniente diferenciar entre los efectos de una hiperglucemia aguda, con aquellos que se observan cuando la hiperglucemia se prolonga a lo largo del tiempo, a fin de establecer analogías, entre el modelo experimental animal, con el síndrome diabético humano, mediante datos de laboratorio y de tipo clínico, de uso habitual en el diagnóstico y manejo de la diabetes humana.
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Acharjee, S., Ghosh, B., Al-Dhubiab, B. E., and Nair, A. B. (2013). Understanding type 1 diabetes: etiology and models. Canadian Journal of Diabetes. 37(4): 269-276.
Al-Awar, A., Kupai, K., Veszelka, M., Szűcs, G., Attieh, Z., Murlasits, Z., …, and Varga, C. (2016). Experimental diabetes mellitus in different animal models. Journal of Diabetes Research. 2016: 9051426.
Arias-Díaz, J. and Balibrea, J. (2007). Modelos animales de intolerancia a la glucosa y diabetes tipo 2. Nutrición Hospitalaria. 22(2): 160-168.
Barbour, L. A. (2019). Metabolic culprits in obese pregnancies and gestational diabetes mellitus: big babies, big twists, big picture: The 2018 Norbert Freinkel Award Lecture. Diabetes Care. 42(5): 718-726.
Barriere, D. A., Noll, C., Roussy, G., Lizotte, F., Kessai, A., Kirby, K., ..., and Sarret, P. (2018). Combination of high-fat/high-fructose diet and low-dose streptozotocin to model longterm type-2 diabetes complications. Scientific Reports. 8(1): 424.
Benomar, Y. and Taouis, M. (2019). Molecular mechanisms underlying obesity-induced hypothalamic inflammation and insulin resistance: pivotal role of resistin/TLR4 pathways. Frontiers in Endocrinology. 10: 140.
Boles, A., Kandimalla, R., and Reddy, P. H. (2017). Dynamics of diabetes and obesity: Epidemiological perspective. Biochimical et Biophysica Acta Molecular Basis Disease. 1863(5): 1026-1036.
Brito-Casillas, Y., Melián, C., and Wägner, A. M. (2016). Study of the pathogenesis and treatment of diabetes mellitus through animal models. Endocrinololgía y Nutrición. 63(7): 345-353.
Burbridge, S., Stewart, I., and Placzek, M. (2016). Development of the neuroendocrine hypothalamus. Comprehensive Physiology. 6(2): 623-643.
Buyukdere, Y., Gulec, A., and Akyol, A. (2019). Cafeteria diet increased adiposity in comparison to high fat diet in young male rats. PeerJ. 7: e6656.
Carrero, J. A., McCarthy, D. P., Ferris, S. T., Wan, X., Hu, H., Zinselmeyer, B. H., …, and Unanue, E. R. (2017). Resident macrophages of pancreatic islets have a seminal role in the initiation of autoimmune diabetes of NOD mice. Proceedings of the National Academy of Sciences of the United States of America. 114(48): E10418-E10427.
Castell-Auví, A., Cedó, L., Pallarès, V., Blay, M., Ardévol, A., and Pinent, M. (2012). The effects of a cafeteria diet on insulin production and clearance in rats. The British Journal of Nutrition. 108(7): 1155-1162.
Chan, M. (2017). Obesity and Diabetes: The Slow-Motion Disaster. Milbank Q. 95(1): 11-14.
Chen, Y. W., Fiscella, K. A., Bacharach, S. Z., and Calu, D. J. (2014). Effect of cafeteria diet history on cue-, pellet-priming-, and stress-induced reinstatement of food seeking infemale rats. PloS One. 9(7): e102213.
Chittka, D., Banas, B., Lennartz, L., Putz, F. J., Eidenschink, K., Beck, S., …, and Banas, M. C. (2018). Long-term expression of glomerular genes in diabetic nephropathy. Nephrology, Dialysis, Transplantation. 33(9): 1533-1544.
Churruca, I., Portillo, M. P., Casis, L., Gutierrez, A., Macarulla, M. T., and Echevarria, E. (2008). Effects of fluoxetine administration on hypothalamic melanocortin system in obese Zucker rats. Neuropeptides. 42(3): 293-299.
Contreras, C. M. and Gutiérrez-García, A. G. (2017). Cognitive impairment in diabetes and poor glucose utilization in the intracellular neural milieu. Med Hypotheses. 104: 160-165.
Contreras, C. M., Gutiérrez-García, A. G., and Moreno-Cortés, M. L. (2019). Responsivity of lateral septum-mPFC connections in alloxan-induced hyperglycemia. Behavioural Brain Research. 368: 111919.
Daryabor, G., Kabelitz, D., and Kalantar, K. (2019). An update on immune dysregulation in obesity-related insulin resistance. Scandinavian Journal of Immunology. 89(4): e12747.
Drel, V. R., Mashtalir, N., Ilnytska, O., Shin, J., Li, F., Lyzogubov, V. V., and Obrosova, I. G. (2006). The leptindeficient (ob/ob) mouse: a new animal model of peripheral neuropathy of type 2 diabetes and obesity. Diabetes. 55(12): 3335-3343.
Dunn, J. S., Sheehan, H. L., and McLetchie, N. G. B. (1943). Necrosis of islets of Langerhans produced experimentally. Lancet. 241 (6242): 484-487.
Federiuk, I. F., Casey, H. M., Quinn, M. J., Wood, M. D., and Ward, W. K. (2004). Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment. Comparative Medicine. 54(3): 252-257.
Flores, Y. N., Contreras, Z. A., Ramirez-Palacios, P., Morales, L. S., Edwards, T. C., Gallegos-Carrillo, K., …, and Patrick, D. L. (2019). Increased prevalence of psychosocial, behavioral, and socio-environmental risk factors among over-weight and obese youths in Mexico and the United States. International Journal of Environmental Research and Public Health. 16(9): E1534.
Fu, Z., Gilbert, E. R., and Liu, D. (2013). Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Current Diabetes Reviews. 9(1): 25-53.
Geiss, L. S., Kirtland, K., Lin, J., Shrestha, S., Thompson, T., Albright, A., and Gregg, E. W. (2017). Changes in diagnosed diabetes, obesity, and physical inactivity prevalence in US counties, 2004-2012. PLoS One. 12(3): e0173428.
Gerber, P. A. and Rutter, G. A. (2017). The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus. Antioxidants & Redox Signaling. 26(10): 501-518.
Gómez-Smith, M., Karthikeyan, S., Jeffers, M. S., Janik, R., Thomason, L. A., Stefanovic, B., and Corbett, D. (2016). A physiological characterization of the Cafeteria diet model of metabolic syndrome in the rat. Physiology and Behavior. 167: 382-391.
Grillo, C. A., Piroli, G. G., Lawrence, R. C., Wrighten, S. A., Green, A. J., Wilson, S. P., ..., and Reagan, L. P. (2015). Hippocampal insulin resistance impairs spatial learning and synaptic plasticity. Diabetes. 64(11): 3927-3936.
Grillo, C. A., Woodruff, J., Macht, V. A., and Reagan, L. P. (2019). Insulin resistance and hippocampal dysfunction: Disentangling peripheral and brain causes from consequences. Experimental Neurology. 318: 71-77.
Guex, C. G., Reginato, F. Z., de-Jesus, P. R., Brondani, J. C., Lopes, G. H. H., and Bauermann, L. F. (2019). Antidiabetic effects of Olea europaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin. Journal of Ethnopharmacology. 235: 1-7.
Gutiérrez, A., Saracibar, G., Casis, L., Echevarria, E., Rodriguez, V. M., Macarulla, M. T., ..., and Portillo, M. P. (2002). Effects of fluoxetine administration on neuropeptide y and orexins in obese zucker rat hypothalamus. Obesity Research. 10(6): 532-540.
Harwood, H. J., Listrani, P., and Wagner, J. D. (2012). Nonhuman primates and other animal models in diabetes research. Journal of Diabetes Science and Technology. 6(3): 503-514.
Hascup, E. R., Broderick, S. O., Russell, M. K., Fang, Y., Bartke, A., Boger, H. A., and Hascup, K. N. (2019). Dietinduced insulin resistance elevates hippocampal glutamate as well as VGLUT1 and GFAP expression in AbetaPP/PS1 mice. Journal of Neurochemistry. 148(2): 219-237.
Heyne, A., Kiesselbach, C., Sahún, I., McDonald, J., Gaiffi, M., Dierssen, M., and Wolffgramm, J. (2009). An animal model of compulsive food-taking behaviour. Addiction Biology. 14(4): 373-383.
Hugés-Hernandorena, B., Rodríguez-García, J. C., Rodríguez-González, J. C., and Marrero-Rodríguez, M. T. (2002). Animales de experimentación como modelos de diabetes mellitus tipo 2. Revista Cubana de Endocrinología. 13(2): 160-168.
Igel, M., Becker, W., Herberg, L., and Joost, H. G. (1997). Hyperleptinemia, leptin resistance, and polymorphic leptin receptor in the New Zealand obese mouse. Endocrinology. 138(10): 4234-4239.
Kahn, S. E., Hull, R. L., and Utzschneider, K. M. (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 444(7121): 840-846.
Karatas, F., Sahin, S., Aytekin, A., Hacioglu, M. B., Imamoglu, G. I., and Altinbas, M. (2018). Durable complete response with a short course of streptozotocin plus doxorubicin combination in malignant metastatic insulinoma. Journal of Cancer Research and Therapeutics. 14(5): 1149-1151.
Kaur, M., Bedi, O., Sachdeva, S., Reddy, B. V. K. K., and Kumar, P. (2014). Rodent animal models: from mild to advanced stages of diabetic nephropathy. Inflammopharmacology. 22(5): 279-293.
Kim, B., Elzinga, S. E., Henn, R. E., McGinley, L. M., and Feldman, E. L. (2019). The effects of insulin and insulin-like growth factor I on amyloid precursor protein phosphorylation in in vitro and in vivo models of Alzheimer’s disease. Neurobiology of Disease. 132: 104541.
Lascar, N., Altaf, Q. A., Raymond, N. T., Broen, J., Pattison, H., Barnett, A., ..., and Bellary, S. (2019). Phenotypic characteristics and risk factors in a multi-ethnic cohort of young adults with type 2 diabetes. Current Medical Research and Opinion. 1-8.
Lenzen, S. (2008). The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 51(2): 216-226.
Lewis, A. R., Singh, S., and Youssef, F. F. (2019). Cafeteria-diet induced obesity results in impaired cognitive functioning in a rodent model. Heliyon. 5(3): e01412.
Liljedahl, L., Norlin, J., McGuire, J. N., and James, P. (2017). Effects of insulin and the glucagon-like peptide 1 receptor agonist liraglutide on the kidney proteome in db/db mice. Physiology Reproduction. 5(6): e13187.
Lucchesi, A. N., Cassettari, L. L., and Spadella, C. T. (2015). Alloxan-induced diabetes causes morphological and ultrastructural changes in rat liver that resemble the natural history of chronic fatty liver disease in humans. Journal of Diabetes Research. 2015: 494578.
Lucchesi, A. N., Freitas, N. T., Cassettari, L. L., Marques, S. F., and Spadella, C. T. (2013). Diabetes mellitus triggers oxidative stress in the liver of alloxan-treated rats: a mechanism for diabetic chronic liver disease. Acta Cirurgica Brasileira. 28(7): 502-508.
Minkowski, O. and Bretzel, R. G. (2002). Further reports on diabetes mellitus after the extirpation of the pancreas. Journal of Molecular Medicine (Berlin, Germany). 80(1): 3-4.
Moreno-Cortés, M. L., Gutiérrez-García, A. G., Guillén-Ruiz, G., Romo-González, T., and Contreras, C. M. (2016). Widespread blunting of hypothalamic and amygdala-septal activity and behavior in rats with long-term hyperglycemia. Behavioural Brain Research. 310: 59-67.
Mtintsilana, A., Micklesfield, L. K., Chorell, E., Olsson, T., and Goedecke, J. H. (2019). Fat redistribution and accumulation of visceral adipose tissue predicts type 2 diabetes risk in middle-aged black South African women: a 13-year longitudinal study. Nutrition and Diabetes. 9(1): 12.
Necyk, C. and Zubach-Cassano, L. (2017). Natural health products and diabetes: a practical review. Canadian Journal of Diabetes. 41(6): 642-647.
Norwitz, N. G., Mota, A. S., Norwitz, S. G., and Clarke, K. (2019). Multi-Loop model of Alzheimer disease: an integrated perspective on the Wnt/GSK3beta, alpha-synuclein, and type 3 diabetes bypotheses. Frontiers in Aging Neuroscience. 11: 184.
Okamura, T., Hashimoto, Y., Hamaguchi, M., Obora, A., Kojima, T., and Fukui, M. (2019). Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: apopulationbased longitudinal study. International Journal of Obesity. 43(1): 139-148.
Ono, H. (2019). Molecular mechanisms of hypothalamic insulin resistance. International Journal of Molecular Sciences. 20(6): E1317.
Ozlu, E., Uzuncakmak, T. K., Takir, M., Akdeniz, N., and Karadag, A. S. (2018). Comparison of cutaneous manifestations in diabetic and nondiabetic obese patients: A prospective, controlled study. Northern Clinics of Istanbul. 5(2): 114-119.
Park, Y. W., Zhu, S., Palaniappan, L., Heshka, S., Carnethon, M. R., and Heymsfield, S. B. (2003). The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Archives International of Medicine. 163(2003): 427-436.
Prakash, L., Bhosale, P., Cloyd, J., Kim, M., Parker, N., Yao, J., ..., and Katz, M. H. (2017). Role of fluorouracil, doxorubicin, and streptozocin therapy in the preoperative treatment of localized pancreatic neuroendocrine tumors. Journal of Gastrointestinal Surgery. 21(1): 155-163.
Radenković, M., Stojanović, M., and Prostran, M. (2016). Experimental diabetes induced by alloxan and streptozotocin: The current state of the art. Journal and Pharmacological and Toxicological Methods. 78: 13-31.
Rawshani, A., Sattar, N., Franzén, S., Rawshani, A., Hattersley, A. T., Svensson, A. M., ..., and Gudbjörnsdottir, S. (2018). Excess mortality and cardiovascular disease in Young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet. 392(10146): 477-486.
Rerup, C. C (1970). Drugs producing diabetes through damage of the insulin secreting cells. Pharmacology Review. 22(4): 485-518.
Sah, S. P., Singh, B., Choudhary, S., and Kumar, A. (2016). Animal models of insulin resistance: A review. Pharmacological Reports: PR. 68(6): 1165-1177.
Saltiel, A. R. and Olefsky, J. M. (2017). Inflammatory mechanisms linking obesity and metabolic disease. Journal Clinical Investigation. 127(1): 1-4.
Sankrityayan, H., Oza, M. J., Kulkarni, Y. A., Mulay, S. R., and Gaikwad, A. B. (2019). ER stress response mediates diabetic microvascular complications. Drug Discovery Today. 1359-6446(19): 30314-30319.
Sharma, G., Ashhar, M. U., Aeri, V., and Katare, D. P. (2019). Development and characterization of late-stage diabetes mellitus and associated vascular complications. Life Sciences. 216: 295-304.
Sharma, K., McCue, P., and Dunn, S. R. (2003). Diabetic kidney disease in the db/db mouse. American Journal of Physiology. Renal Physiology. 284(6): F1138-F1144.
Shivaswamy, V., Boerner, B., and Larsen, J. (2016). Post-Transplant diabetes mellitus: causes, treatment, and impact on outcomes. Endocrinology Review. 37(1): 37-61.
Soto, M., Cai, W., Konishi, M., and Kahn, C. R. (2019). Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior. Proceeding of the National Academy of Sciences of the United States America. 116(13): 6379-6384.
Spurr, S., Bally, J., Allan, D., Bullin, C., and McNair, E. (2019). Prediabetes: An emerging public health concern in adolescents. Endocrinology, Diabetes and Metabolism. 2(2): e00060.
Srinivasan, K. and Ramarao, P. (2007). Animal models in type 2 diabetes research: an overview. The Indian of Journal of Medical Research. 125(3): 451-472.
Staats, J. (1975). Diabetes in the mouse due to two mutan genes - a bibliography. Diabetologia. 11(4): 325-327.
Stein, A. D., Obrutu, O. E., Behere, R. V., and Yajnik, C. S. (2019). Developmental undernutrition, offspring obesity and type 2 diabetes. Diabetologia. 62(10): 1773-1778.
Szkudelski, T. (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research. 50(6): 537-546.
Tamas, M. J., Khakharia, A., Rothenberg, R. B., and Phillips, L. S. (2018). Weight trends in veterans with and without diabetes, 2000 to 2014. Obesity. 26(12): 1949-1957.
Tancredi, M., Rosengren, A., Svensson, A. M., Kosiborod, M., Pivodic, A., Gudbjörnsdottir, S., …, and Lind, M. (2015).
Excess mortality among persons with Type 2 diabetes. The New England Journal of Medical. 373(18): 1720-1732.
Waernbaum, I., Dahlquist, G., and Lind, T. (2019). Perinatal risk factors for type 1 diabetes revisited: a populationbased register study. Diabetologia. 1-12.
Wells, J. C. K. (2019). The diabesity epidemic in the light of evolution: insights from the capacity-load model. Diabetologia. 62(10): 1740-1750.
Wilson, R. D. and Islam, M. S. (2012). Fructose-fed streptozotocin-injected rat: an alternative model for type 2 diabetes. Pharmacological Reports: PR. 64(1): 129-139.
Winocur, G., Greenwood, C. E., Piroli, G. G., Grillo, C. A., Reznikov, L. R., Reagan, L. P., and McEwen, B. S. (2005). Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity. Behavioral Neuroscience. 119(5): 1389-1395.
Wojciechowska, J., Krajewski, W., Bolanowski, M., Kręcicki, T., and Zatoński, T. (2016). Diabetes and Cancer: a review of current knowledge. Experimental Clinical Endocrinology Diabetes. 124(5): 263-275.
Yu, Y. B., Bian, J. M., and Gu, D. H. (2015). Transplantation of insulin-producing cells to treat diabetic rats after 90 % pancreatectomy. World Journal of Gastroenterology. 21(21): 6582-6590.
Zhou, W., Wei, L., Xiao, T., Lai, C., Peng, M., Xu, L., …, and Zhang, F. (2017). Diabetogenic agent alloxan is a proteasome inhibitor. Biochemical and Biophysical Research Communications. 488(2): 400-406.
