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A comparison of metabolomic changes in type-1 diabetic C57BL/6N mice originating from different sources

Abstract

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

References

  1. Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003; 17(1): 24–38.

    Article  CAS  PubMed  Google Scholar 

  2. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2014; 37 Suppl 1: S81–90.

    Article  Google Scholar 

  3. Chao KC, Chao KF, Fu YS, Liu SH, Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One 2008; 3(1): e1451.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Diabetes Prevention Trial—Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 2002; 346(22): 1685–1691.

    Article  Google Scholar 

  5. van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 2011; 91(1): 79–118.

    Article  PubMed  CAS  Google Scholar 

  6. Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK, Environmental triggers and determinants of type 1 diabetes. Diabetes 2005; 54 Suppl 2: S125–136.

    Article  CAS  PubMed  Google Scholar 

  7. Skyler JS, Cefalu WT, Kourides IA, Landschulz WH, Balagtas CC, Cheng SL, Gelfand RA, Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study. Lancet 2001; 357(9253): 331–335.

    Article  CAS  PubMed  Google Scholar 

  8. Polat K, Günes S. An expert system approach based on principal component analysis and adaptive neuro-fuzzy inference system to diagnosis of diabetes disease. Digital Signal Processing 2007; 17(4): 702–710.

    Article  Google Scholar 

  9. Oelze M, Knorr M, Schuhmacher S, Heeren T, Otto C, Schulz E, Reifenberg K, Wenzel P, Münzel T, Daiber A. Vascular dysfunction in streptozotocin-induced experimental diabetes strictly depends on insulin deficiency. J Vasc Res 2011; 48(4): 275–284.

    Article  CAS  PubMed  Google Scholar 

  10. Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51(2): 216–226.

    Article  CAS  PubMed  Google Scholar 

  11. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol Res 2001; 50(6): 537–546.

    CAS  PubMed  Google Scholar 

  12. Eleazu CO, Eleazu KC, Chukwuma S, Essien UN, Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord 2013; 12(1): 60.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Kolb H. Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice. Diabetes Metab Rev 1987; 3(3): 751–778.

    Article  CAS  PubMed  Google Scholar 

  14. Like AA, Rossini AA, Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 1976; 193(4251): 415–417.

    Article  CAS  PubMed  Google Scholar 

  15. Wu KK, Huan Y. Diabetic atherosclerosis mouse models. Atherosclerosis 2007; 191(2): 241–249.

    Article  CAS  PubMed  Google Scholar 

  16. Weide LG, Lacy PE, Low-dose streptozocin-induced autoimmune diabetes in islet transplantation model. Diabetes 1991; 40(9): 1157–1162.

    Article  CAS  PubMed  Google Scholar 

  17. REITMAN S, FRANKEL S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957; 28(1): 56–63.

    Article  CAS  PubMed  Google Scholar 

  18. Motyl K, McCabe LR, Streptozotocin, type I diabetes severity and bone. Biol Proced Online 2009; 11: 296–315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fontaine DA, Davis DB, Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium. Diabetes 2016; 65(1): 25–33.

    Article  CAS  PubMed  Google Scholar 

  20. Collins S, Martin TL, Surwit RS, Robidoux J. Genetic vulnerability to diet-induced obesity in the C57BL/6J mouse: physiological and molecular characteristics. Physiol Behav 2004; 81(2): 243–248.

    Article  CAS  PubMed  Google Scholar 

  21. Winzell MS, Ahrén B. The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 2004; 53 Suppl 3: S215–219.

    Article  PubMed  Google Scholar 

  22. Mashimo T, Serikawa T. Rat resources in biomedical research. Curr Pharm Biotechnol 2009; 10(2): 214–220.

    Article  CAS  PubMed  Google Scholar 

  23. Croy BA, The 1999 Reginald Thomson Lecture. Custom-built mice: unique discovery tools in biomedical research. Can Vet J 2000; 41(3): 201–206.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ardaillou R. [Transgenic mice: a major advance in biomedical research]. Bull Acad Natl Med 2009; 193(8): 1773–1782.

  25. Sundberg JP, Schofield PN, Commentary: mouse genetic nomenclature. Standardization of strain, gene, and protein symbols. Vet Pathol 2010; 47(6): 1100–1104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Junod A, Lambert AE, Stauffacher W, Renold AE, Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 1969; 48(11): 2129–2139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE, Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med 1967; 126(1): 201–205.

    Article  CAS  PubMed  Google Scholar 

  28. Furman BL, Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc Pharmacol 2015; 70: 5.47.1–20.

    Article  Google Scholar 

  29. Habibuddin M, Daghriri HA, Humaira T, Al Qahtani MS, Hefzi AA, Antidiabetic effect of alcoholic extract of Caralluma sinaica L. on streptozotocin-induced diabetic rabbits. J Ethnopharmacol 2008; 117(2): 215–220.

    Article  CAS  PubMed  Google Scholar 

  30. Lee SI, Kim JS, Oh SH, Park KY, Lee HG, Kim SD, Antihyperglycemic effect of Fomitopsis pinicola extracts in streptozotocin-induced diabetic rats. J Med Food 2008; 11(3): 518–524.

    Article  CAS  PubMed  Google Scholar 

  31. Merzouk H, Madani S, Chabane Sari D, Prost J, Bouchenak M, Belleville J. Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes. Clin Sci (Lond) 2000; 98(1): 21–30.

    Article  CAS  Google Scholar 

  32. Ohno T, Horio F, Tanaka S, Terada M, Namikawa T, Kitoh J. Fatty liver and hyperlipidemia in IDDM (insulin-dependent diabetes mellitus) of streptozotocin-treated shrews. Life Sci 2000; 66(2): 125–131.

    Article  CAS  PubMed  Google Scholar 

  33. Grill V, Björkman O, Gutniak M, Lindqvist M. Brain uptake and release of amino acids in nondiabetic and insulin-dependent diabetic subjects: important role of glutamine release for nitrogen balance. Metabolism 1992; 41(1): 28–32.

    Article  CAS  PubMed  Google Scholar 

  34. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP, A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009; 9(4): 311–326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shah SH, Crosslin DR, Haynes CS, Nelson S, Turer CB, Stevens RD, Muehlbauer MJ, Wenner BR, Bain JR, Laferrère B, Gorroochurn P, Teixeira J, Brantley PJ, Stevens VJ, Hollis JF, Appel LJ, Lien LF, Batch B, Newgard CB, Svetkey LP, Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia 2012; 55(2): 321–330.

    Article  CAS  PubMed  Google Scholar 

  36. McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, Clish CB, Mootha VK, Grinspoon SK, Fleischman A. Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes 2013; 8(1): 52–61.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Young-Suk Jung.

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Lee, S., Kwak, JH., Kim, S.H. et al. A comparison of metabolomic changes in type-1 diabetic C57BL/6N mice originating from different sources. Lab Anim Res 34, 232–238 (2018). https://doi.org/10.5625/lar.2018.34.4.232

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  • DOI: https://doi.org/10.5625/lar.2018.34.4.232

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