A comparison of metabolomic changes in type-1 diabetic C57BL/6N mice originating from different sources
- 9 Downloads
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.
KeywordsType-1 diabetes streptozotocin C57BL/6N branched-chain amino acids
- 2.American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2014; 37 Suppl 1: S81–90.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.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.Google Scholar
- 24.Ardaillou R. [Transgenic mice: a major advance in biomedical research]. Bull Acad Natl Med 2009; 193(8): 1773–1782.Google Scholar
- 28.Furman BL, Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc Pharmacol 2015; 70: 5.47.1–20.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.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.PubMedPubMedCentralGoogle 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.PubMedGoogle 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.PubMedGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.