DIFFERENT EXPERIMENTAL MODELS USED TO INDUCE DIABETES MELLITUS IN RODENTS: A REVIEW
Keywords:Insulin resistance, Alloxan, Streptozotocin, High fat diet
Diabetes is a metabolic disease characterized by the presence of hyperglycemia resulting from either defects in insulin secretion or action or both. Various processes are involved in the development of diabetes. These range from autoimmune destruction of the insulin-producing cells, β-cells of the pancreas, a dysfunction of the pancreatic β-cell, and impaired insulin action through insulin resistance. Experimental diabetes in animals are widely induced by administration of alloxan and streptozotocin at a proper dose. The mechanism of their action in pancreatic β-cells has been extensively investigated. Reactive oxygen species are responsible for the cytotoxic action of both these diabetogenic agents. However, the source of their generation is different in the case of alloxan (ALX) and streptozotocin (STZ). In one of the study, it is also showed that the administration of a high-fat diet (HFD) to rats for 16 w showed a progressive increase in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia and hyperinsulinemia. Administration of alloxan or streptozotocin in addition with HFD is also able to induce diabetes in an experimental rat model.
2. WHO Expert Committee on Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications; 1999. p. 1-59.
3. Jun Y, Shen J, Sun TT, Zhang X, Wong N. Obesity, insulin resistance, NASH and Hepatocellular carcinoma, Seminars in cancer biology; 2013.
4. Sheehan HL, McLetchie NGB. Necrosis of islets of langerhans produced experimentally. Lancet 1943;1:484-7.
5. Islam MS, DuLoots T. Experimental rodent models of type 2 diabetes: a review. Methods Find Exp Clin Pharmacol 2009;31:249–61.
6. Liu RH, Mizuta M, Kurose T, Matsukura S. Early events involved in the development of insulin resistance in zucker fatty rat. Int J Obes Relat Metab Disord 2002;26:318–26.
7. Dourmashkin JT, Chang GQ, Gayles EC, Hill JO, Fried SK, Julien C, et al. Different forms of obesity as a function of diet composition. Int J Obes (Lond) 2005;29:1368–78.
8. Jacobs HR. Hypoglycemic action of alloxan. Proc Soc Exp Biol Med 1937;37:407-9.
9. Bailey CC, Bailey OT. The production of diabetes mellitus in rabbits with alloxan. J Am Med Assoc 1943;122:1165-6.
10. Brunschwig A, Goldner MG, Allen JG, Gomori G. Alloxan. J Am Med Assoc 1943;122:966.
11. Dunn JS, McLetchie NGB. Experimental alloxan diabetes in the rat. Lancet 1943;2:384-7.
12. Goldncr MG, Gomori G. Alloxan diabetes mellitus in the dog. Endocrinology 1943;33:297-308.
13. Gomori G, Goldner MG. Production of diabetes mellitus in rats with alloxan. Proc Soc Exp Biol Med 1943;54:287-90.
14. Etuk EUNJ. Animals models for studying diabetes mellitus. Agric Biol 2010;1:130-4.
15. Iranloye BO, Arikawe AP, Rotimi G, Sogbade AO. Anti-diabetic and anti-oxidant effects of zingiber officinale on alloxan-induced and insulin-resistant diabetic male rats. Physiol Soc Nigeria 2011;26:89-96.
16. Eizirik dl, Pipeleers Dg, Ling Z, Welsh N, Hellerstrom C, Andersson A. Major species differences between humans and rodents in the susceptibility to pancreatic beta-cell injury. Proc Natl Acad Sci USA 1994;91:9253-6.
17. Gruppuso PA, Boylan JM, Posner BI, Faure R, Brautigan DL. Hepatic protein phosphotyrosine phosphatase. Dephosphorylation of insulin receptor and epidermal growth factor receptors in normal and alloxan diabetic rats. J Clin Invest 1990;85:1754-60.
18. Katsumata K, Katsumata KJr, Katsumata Y. Protective effect of Diltiazem hydrochloride on the occurrence of alloxan-or streptozotocin-induced diabetes in rats. Horm Metab Res 1992;24:508-10.
19. Lenzen S, Munday R. Thiol-group reactivity, hydrophilicity and stability of alloxan, its reduction products and its N-methyl derivatives and a comparison with ninhydrin. Biochem Pharmacol 1991;42:1385-91.
20. Zhang H, Zdolsek JM, Brunk UT. Alloxan cytotoxicity involves lysosomal damage. APMIS1992;100:309-16.
21. Munday R. Dialuric acid autoxidation. Effects of transition metals on the reaction rate and on the generation of "active oxygen" species. Biochem Pharmacol 1988;37:409-13.
22. Das J, Vasan V, Sil PC. Taurine exerts a hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis. Toxicol Appl Pharmacol 2012;258:296-308.
23. Herr RR, Jahnke JK, Argoudelis AD. The structure of streptozotocin. J Am Chem Soc 1967;89:4808-9.
24. Ganda OP, Rossi AA, Like AA. Studies on streptozotocin diabetes. Diabetes 1976;25:595-603.
25. Katsumata K, Katsumata KJr, Katsumata Y. Protective effect of diltiazem hydrochloride on the occurrence of alloxan-or streptozotocin-induced diabetes in rats. Horm Metab Res 1992;24:508-10.
26. Portha B, Levacher C, Picon L, Rosselin G. Diabetogenic effect of streptozotocin in the rat during the perinatal period. Diabetes 1974;23:889-95.
27. Mythili MD, Vyas R, Akila G, Gunasekaran S. Effect of streptozotocin on the ultrastructure of rat pancreatic islets. Microsc Res Tech 2004;63:274-81.
28. Patel R, Shervington A, Pariente JA, Martinez Burgos MA, Salido GM, Adeghate E, et al. Mechanism of exocrine pancreatic insufficiency in streptozotocin-induced type 1 diabetes mellitus. Ann NY Acad Sci 2006;1084:71-88.
29. Centro de prensa de la Organización Mundial de la Salud. Obesidad y sobrepeso. Available from: http://www.who.int/ mediacentre/factsheets/fs311/e/. [Last accessed on 16 Jun 2019].
30. Almanza MR, Gomez RC, Torres JFM. Obesity and type 2 diabetes: also linked in therapeutic options. Endocrinol Diabetes Nutr 2019;66:140-9.
31. Shafrir E. Diabetes in animals: contribution to the understanding of diabetes by the study of its etiopathology in animal models. In: Porte D, Sherwin RS, Baron A. editors. Diabetes mellitus. NewYork: McGraw-Hill; 2003. p. 231–55.
32. Rerup CC. Drugs producing diabetes through damage of the insulin-secreting cells. Pharmacol Rev 1970;22:485–518.
33. Storlien LH, James DE, Burleigh KM, Chisholm DJ, Kraegen EW. Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure and obesity in the rat. Am J Physiol 1986;251:576–83.
34. Srinivasan K, Patole PS, Kaul CL, Ramarao P. Reversal of glucose intolerance by pioglitazone in high-fat diet fed rats. Methods Find Exp Clin Pharmacol 2004;26:327–33.
35. Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390–4.
36. Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390–4.
37. K Srinivasan, B Viswanad, L Asrat, CL Kaul, P Ramarao. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res 2005;52:313–20.
38. Reaven GM. Insulin resistance, hyperinsulinemia, hypertriglyceridemia and hypertension: parallels between human disease and rodent models. Diabetes Care 1991;14:195–202.
39. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose-fatty acid cycle. Its role in insulin sensitivity and metabolic disturbances in diabetes mellitus. Lancet 1963;1:785–9.
40. Belfiore F, Iannello S. Insulin resistance in obesity: metabolic mechanisms and measurement methods. Mol Gen Metab 1998;65:121-8.
41. Iwanishi M, Kobayashi M. Effect of pioglitazone on insulin receptors of skeletal muscles from high-fat-fed rats. Metabolism 1993;42:1017–21.
42. Rosholt MN, King PA, Horton ES. High-fat diet reduces glucose transporter responses to both insulin and exercise. Am J Physiol 1994;266:95–101.
43. Li-Qin Tang, Wei Wei, Li-Ming Chen, Sheng Liu. Effects of berberine on diabetes induced by alloxan and a high-fat/high-cholesterol diet in rats. J Ethnopharmacol 2006;108:109–15.