Experimental models of type 1 diabetes

Cover Page


Cite item

Full Text

Abstract

This article describes currently used experimental animal models of type 1 diabetes. The literature data on the pathogenesis of clinical and morphological patterns of the disease and the possibility of extrapolation have been summarized in the review. In addition, the advantages and disadvantages of each of the models have been evaluated. Based on the reported results, it can be concluded that preclinical research is essential as fundamental basis for the investigation of type 1 diabetes mellitus.

About the authors

Maria I. Yarmolinskaya

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott; North-Western State Medical University named after I.I. Mechnikov

Email: m.yarmolinskaya@gmail.com
SPIN-code: 3686-3605
Scopus Author ID: 489874

MD, PhD, DSci (Medicine), Professor of the Russian Academy of Sciences, the Head of the Department of Endocrinology of Reproduction, the Head of the Diagnostics and Treatment of Endometriosis Center; Professor. The Department of Obstetrics and Gynecology

Russian Federation, Saint Petersburg

Nelly Yu. Andreyeva

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Author for correspondence.
Email: Nelly8352@yahoo.com

Resident Doctor

Russian Federation, Saint Petersburg

Elena I. Abashova

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: abashova@yandex.ru
SPIN-code: 2133-0310
Scopus Author ID: 252499

MD, PhD, Senior Researcher. The Department of Endocrinology of Reproduction

Saint Petersburg

Elena V. Misharina

The Research Institute of Obstetrics, Gynecology, and Reproductology named after D.O. Ott

Email: mishellena@gmail.com

MD, PhD, Senior Researcher. The Department of Endocrinology of Reproduction

Russian Federation, Saint Petersburg

References

  1. Ostrauskas R. The prevalence of type 1 diabetes mellitus among 15-34-year-aged Lithuanian inhabitants during 1991-2010. Prim Care Diabetes. 2015;9(2):105-111. https://doi.org/10.1016/j.pcd.2014.07.009.
  2. Дедов И.И., Шестакова М.В. Сахарный диабет и артериальная гипертензия. — М., 2006. — 344 с. [Dedov II, Shestakova MV. Sakharnyy diabet i arterial’naya gipertenziya. Moscow; 2006. 344 p. (In Russ.)]
  3. Roglic G, Unwin N, Bennett PH, et al. The burden of mortality attributable to diabetes: realistic estimates for the year 2000. Diabetes Care. 2005;28(9):2130-2135. https://doi.org/10.2337/diacare.28.9.2130.
  4. Дедов И.И., Шестакова М.В. Сахарный диабет и репродуктивная система. — М., 2016. — 176 с. [Dedov II, Shestakova MV. Sakharnyy diabet i reproduktivnaya sistema. Moscow; 2016. 176 p. (In Russ.)]
  5. Потин В.В., Боровик Н.В., Тиселько А.В. Сахарный диабет и репродуктивная система женщины // Журнал акушерства и женских болезней. — 2006. — Т. 55. — № 1. — C. 85–90. [Potin VV, Borovik NV, Tisel’ko AV. Diabetes Mellitus And Female Reproductive System. Journal of Obstetrics and Womenʼs Diseases. 2006;55(1):85-90. (In Russ.)]
  6. Levy N. The use of animal as models: ethical considerations. Int J Stroke. 2012;7(5):440-442. https://doi.org/10.1111/j.1747-4949.2012.00772.x.
  7. Kroeger M. How omics technologies can contribute to the ‘3R’ principles by introducing new strategies in animal testing. Trends Biotechnol. 2006;24(8):343-346. https://doi.org/10.1016/j.tibtech.2006.06.003.
  8. Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Med. 2005;22(4):359-370. https://doi.org/10.1111/j.1464-5491.2005.01499.x.
  9. Etuk E. Animals models for studying diabetes mellitus. Agric Biol J N Am. 2010;1(2):130-4.
  10. Баранов В.Г. Экспериментальный сахарный диабет. — Л.: Наука, 1983. — 240 с. [Baranov VG. Eksperimental’nyy sakharnyy diabet. Leningrad: Nauka; 1983. 240 p. (In Russ.)]
  11. Anderson MS, Bluestone JA. The NOD mouse: a model of immune dysregulation. Annu Rev Immunol. 2005;23:447-485. https://doi.org/10.1146/annurev.immunol.23.021704.115643.
  12. Saxena V, Ondr JK, Magnusen AF, et al. The countervailing actions of myeloid and plasmacytoid dendritic cells control autoimmune diabetes in the nonobese diabetic mouse. J Immunol. 2007;179(8):5041-5053. https://doi.org/10.4049/jimmunol.179.8.5041.
  13. Jayasimhan A, Mansour KP, Slattery RM. Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons from the NOD mouse. Clin Sci (Lond). 2014;126(1):1-18. https://doi.org/10.1042/CS20120627.
  14. You S, Chatenoud L. Autoimmune diabetes: An overview of experimental models and novel therapeutics. Methods Mol Biol. 2016;1371:117-142. https://doi.org/10.1007/978-1-4939-3139-2_8.
  15. Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002;347(12):911-920. https://doi.org/10.1056/NEJMra020100.
  16. Markle JG, Frank DN, Mortin-Toth S, et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084-1088. https://doi.org/10.1126/science.1233521.
  17. Pozzilli P, Signore A, Williams AJK, Beales PE. NOD mouse colonies around the world- recent facts and figures. Immunol today. 1993;14(5):193-196. https://doi.org/10.1016/0167-5699(93)90160-m.
  18. Adorini L, Gregori S, Harrison LC. Understanding autoimmune diabetes: insights from mouse models. Trends Mol Med. 2002;8(1):31-38. https://doi.org/10.1016/s1471-4914(01)02193-1.
  19. Baxter AG, Duckworth RC. Models of type 1 (autoimmune) diabetes. Drug Discov Today Dis Models. 2004;1(4):451-455. https://doi.org/10.1016/j.ddmod.2004.11.012.
  20. Besançon A, Goncalves T, Valette F, et al. A selective CD28 antagonist and rapamycin synergise to protect against spontaneous autoimmune diabetes in NOD mice. Diabetologia. 2018;61(8):1811-1816. https://doi.org/10.1007/s00125-018-4638-7.
  21. Montanucci P, Pescara T, Alunno A, et al. Remission of hyperglycemia in spontaneously diabetic NOD mice upon transplant of microencapsulated human umbilical cord Wharton jelly‐derived mesenchymal stem cells (hUCMS). Xenotransplantation. 2018:e12476. https://doi.org/10.1111/xen.12476.
  22. Fiorina P, Tahvili S, Törngren M, et al. Paquinimod prevents development of diabetes in the non-obese diabetic (NOD) mouse. Plos One. 2018;13(5):e0196598. https://doi.org/10.1371/journal.pone.0196598.
  23. Mathews CE. Utility of murine models for the study of spontaneous autoimmune type 1 diabetes. Pediatr Diabetes. 2005;6(3):165-177. https://doi.org/10.1111/j.1399-543X.2005.00123.x.
  24. Li Y, Zhou L, Li Y, et al. Identification of autoreactive CD8+ T cell responses targeting chromogranin A in humanized NOD mice and type 1 diabetes patients. Clin Immunol. 2015;159(1):63-71. https://doi.org/10.1016/j.clim.2015.04.017.
  25. Kachapati K, Adams D, Bednar K, Ridgway WM. The non-obese diabetic (NOD) mouse as a model of human type 1 diabetes. 2012:3-16. https://doi.org/10.1007/978-1-62703-068-7_1.
  26. Mordes JP, Bortell R, Blankenhorn EP, et al. Rat models of type 1 diabetes: genetics, environment, and autoimmunity. ILAR J. 2004;45(3):278-291. https://doi.org/10.1093/ilar.45.3.278.
  27. Crisá L, Mordes JP, Rossini AA. Autoimmune diabetes mellitus in the BB rat. Diabetes Metab Rev. 1992;8(1):9-37. https://doi.org/10.1002/dmr.5610080104.
  28. Lally FJ, Ratcliff H, Bone AJ. Apoptosis and disease progression in the spontaneously diabetic BB/S rat. Diabetologia. 2001;44(3):320-324. https://doi.org/10.1007/s001250051621.
  29. Bortel R, Waite DJ, Whalen BJ, et al. Levels of Art2+ cells but not soluble Art2 protein correlate with expression of autoimmune diabetes in the BB rat. Autoimmunity. 2001;33(3):199-211. https://doi.org/10.3109/08916930109008047.
  30. Kim JM, Lee TH, Lee MC, et al. Endoneurial microangiopathy of sural nerve in experimental vacor-induced diabetes. Ultrastruct Pathol. 2002;26(6):393-401. https://doi.org/10.1080/01913120290104700.
  31. Monago CC, Onwuka F, Osaro E. Effect of combined therapy of diabinese and nicotinic acid on liver enzymes in rabbits with dithizone-induced diabetes. J Exp Pharmacol. 2010;2:145-153. https://doi.org/10.2147/JEP.S11490.
  32. Bailey CC, Bailey OT, Leech RS. Diabetes mellitus in rabbits injected with dialuric acid. Proc Soc Exp Biol Med. 1946;63(3):502-505. https://doi.org/10.3181/00379727-63-15651
  33. Wöhler F, Liebig J. Untersuchungen über die Natur der Harnsäure. Annalen der Pharmacie. 1838;26(3):241-336. https://doi.org/10.1002/jlac.18380260302.
  34. Shaw Dunn J, McLetchie NGB. Experimental alloxan diabetes in the rat. Lancet. 1943;242(6265):384-387. https://doi.org/10.1016/s0140-6736(00)87397-3.
  35. Dunn JS, Kirkpatrick J, McLetchie NGB, Telfer SV. Necrosis of the islets of Langerhans produced experimentally. J Pathol Bacteriol. 1943;55(3):245-257. https://doi.org/10.1002/path.1700550302.
  36. Goldner MG, Gomori G. Alloxan diabetes in the Dog1. Endocrinology. 1943;33(5):297-308. https://doi.org/ 10.1210/endo-33-5-297.
  37. 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(7):1385-1391. https://doi.org/10.1016/0006-2952(91)90449-f.
  38. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia. 2008;51(2):216-226. https://doi.org/10.1007/s00125-007-0886-7.
  39. Gorus FK, Malaisse WJ, Pipeleers DG. Selective uptake of alloxan by pancreatic B-cells. Biochem J. 1982;208(2):513-515. https://doi.org/10.1042/bj2080513.
  40. Boquist L, Nelson L, Lorentzon R. Uptake of labeled alloxan in mouse organs and mitochondria in vivo and in vitro. Endocrinology. 1983;113(3):943-948. https://doi.org/10.1210/endo-113-3-943.
  41. Lenzen S, Panten U. Alloxan: history and mechanism of action. Diabetologia. 1988;31(6):337-342. https://doi.org/10.1007/bf02341500.
  42. Tiedge M, Richter T, Lenzen S. Importance of cysteine residues for the stability and catalytic activity of human pancreatic beta cell glucokinase. Arch Biochem Biophys. 2000;375(2):251-260. https://doi.org/10.1006/abbi.1999.1666.
  43. Borg LAH. Effects of alloxan on the islets of Langerhans inhibition of leucine metabolism and insulin secretion. Biochim Biophys Acta Gen Subj. 1981;677(2):257-262. https://doi.org/10.1016/0304-4165(81)90093-3.
  44. Cohen G, Heikkila RE. The generation of hydrogen peroxide, superoxide radical, and hydroxyl radical by 6-hydroxydopamine, dialuric acid, and related cytotoxic agents. J Biol Chem. 1974;249(8):2447-2452.
  45. Winterbourn CC, Cowden WB, Sutton HC. Auto-oxidation of dialuric acid, divicine and isouramil. Biochem Pharmacol. 1989;38(4):611-618. https://doi.org/10.1016/0006-2952(89)90206-2.
  46. Winterbourn CC, Munday R. Glutathione-mediated redox cycling of alloxan. Biochem Pharmacol. 1989;38(2):271-277. https://doi.org/10.1016/0006-2952(89)90037-3.
  47. Kim H-R, Rho H-W, Park B-H, et al. Role of Ca2+ in alloxan-induced pancreatic β-cell damage. Biochim Biophys Acta Mol Basis Dis. 1994;1227(1-2):87-91. https://doi.org/10.1016/0925-4439(94)90111-2.
  48. Park BH, Rho HW, Park JW, et al. Protective mechanism of glucose against alloxan-induced pancreatic beta-cell damage. Biochem Biophys Res Commun. 1995;210(1):1-6. https://doi.org/10.1006/bbrc.1995.1619.
  49. Weaver DC, McDaniel ML, Naber SP, et al. Alloxan stimulation and inhibition of insulin release from isolated rat islets of Langerhans. Diabetes. 1978;27(12):1205-1214. https://doi.org/10.2337/diab.27.12.1205.
  50. Wrenshall GA, Collins-Williams J, Best CH. Initial changes in the blood sugar of the fasted anesthetized dog after alloxan. Am J Physiol. 1950;160(2):228-246. https://doi.org/10.1152/ajplegacy.1950.160.2.228.
  51. Tasaka Y, Inoue Y, Matsumoto H, Hirata Y. Changes in plasma glucagon, pancreatic polypeptide and insulin during development of alloxan diabetes mellitus in dog. Endocrinol Jpn. 1988;35(3):399-404. https://doi.org/10.1507/endocrj1954.35.399.
  52. Macedo CS, Capelletti SM, Mercadante CS, et al. Experimental model of induction of diabetes mellitus in rats. In: Plastic surgery, laboratory of plastic surgery. Sao Paulo: Paulista School of Medicine; 2005. P. 2-15.
  53. Lenzen S, Tiedge M, Jörns A, Munday R. Alloxan derivatives as a tool for the elucidation of the mechanism of the diabetogenic action of alloxan. In: Lessons from Animal Diabetes VI. Ed. by E. Shafrir. Boston: Birkhäuser; 1996. P. 113-122. https://doi.org/10.1007/978-1-4612-4112-6_8.
  54. Favaro RR, Salgado RM, Covarrubias AC, et al. Long-term type 1 diabetes impairs decidualization and extracellular matrix remodeling during early embryonic development in mice. Placenta. 2013;34(12):1128-1135. https://doi.org/10.1016/j.placenta.2013.09.012.
  55. Irshad N, Akhtar MS, Bashir S, et al. Hypoglycaemic effects of methanolic extract of Canscora decussata (Schult) whole-plant in normal and alloxan-induced diabetic rabbits. Pak J Pharm Sci. 2015;28(1):167-174.
  56. Sodha NR, Boodhwani M, Clements RT, et al. Increased antiangiogenic protein expression in the skeletal muscle of diabetic swine and patients. Arch Surg. 2008;143(5):463-470. https://doi.org/10.1001/archsurg.143.5.463.
  57. Federiuk IF, Casey HM, Quinn MJ, et al. Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment. Comp Med. 2004;54(3):252-257.
  58. Sano T, Ozaki K, Terayama Y, et al. A novel diabetic murine model of Candida albicans-induced mucosal inflammation and proliferation. J Diabetes Res. 2014;2014:509325. https://doi.org/10.1155/2014/509325.
  59. Reis FPd, Sementilli A, Gagliardi ARdT. Experimental diabetes exacerbates skin transplant rejection in rats. Acta Cir Bras. 2013;28(5):323-326. https://doi.org/10.1590/s0102-86502013000500001.
  60. Kumar S, Singh R, Vasudeva N, Sharma S. Acute and chronic animal models for the evaluation of anti-diabetic agents. Cardiovasc Diabetol. 2012;11:9. https://doi.org/10.1186/1475-2840-11-9.
  61. Radenkovic M, Stojanovic M, Prostran M. Experimental diabetes induced by alloxan and streptozotocin: The current state of the art. J Pharmacol Toxicol Methods. 2016;78:13-31. https://doi.org/10.1016/j.vascn.2015.11.004.
  62. Chatzigeorgiou A, Halapas A, Kalafatakis K, Kamper E. The use of animal models in the study of diabetes mellitus. In Vivo. 2009;23(2):245-258.
  63. Vargas L, Friederici HHR, Maibenco HC. Cortical sponge kidneys induced in rats by alloxan. Diabetes. 1970;19(1):33-44. https://doi.org/10.2337/diab.19.1.33.
  64. Malaisse WJ, Malaisse-Lagae F, Sener A, Pipeleers DG. Determinants of the selective toxicity of alloxan to the pancreatic B cell. PNAS. 1982;79(3):927-930. https://doi.org/10.1073/pnas.79.3.927.
  65. Tiedge M, Lortz S, Drinkgern J, Lenzen S. Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells. Diabetes. 1997;46(11):1733-1742. https://doi.org/10.2337/diab.46.11.1733.
  66. Srinivasan K, Ramarao P. Animal model in type 2 diabetes research: An overview. Ind J Med Res. 2007;125(3):451.
  67. Islam MS, Loots du T. Experimental rodent models of type 2 diabetes: a review. Methods Find Exp Clin Pharmacol. 2009;31(4):249-261. https://doi.org/10.1358/mf.2009.31.4.1362513.
  68. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res. 2001;50(6):537-546.
  69. Turk J, Corbett JA, Ramanadham S, et al. Biochemical evidence for nitric oxide formation from streptozotocin in isolated pancreatic islets. Biochem Biophys Res Commun. 1993;197(3):1458-1464. https://doi.org/10.1006/bbrc.1993.2641.
  70. Bedoya FJ, Solano F, Lucas M. N-Monomethyl-arginine and nicotinamide prevent streptozotocin-induced double strand DNA break formation in pancreatic rat islets. Experientia. 1996;52(4):344-347. https://doi.org/10.1007/ bf01919538.
  71. Dekel Y, Glucksam Y, Elron-Gross I, Margalit R. Insights into modeling streptozotocin-induced diabetes in ICR mice. Lab Anim (NY). 2009;38(2):55-60. https://doi.org/10.1038/laban0209-55.
  72. Kazumi T, Yoshino G, Fujii S, Baba S. Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Cancer Res. 1978;38(7):2144-2147.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2019 Yarmolinskaya M.I., Andreyeva N.Y., Abashova E.I., Misharina E.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies