Lab Anim Res.  2018 Dec;34(4):232-238. 10.5625/lar.2018.34.4.232.

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

• Lee S
• Kwak JH
• Kim SH
• Yun J
• Cho JY
• Kim K
• Hwang D
• Jung YS

• KMID: 2459300
• DOI: http://doi.org/10.5625/lar.2018.34.4.232

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.

Keyword

Type-1 diabetes; streptozotocin; C57BL/6N; branched-chain amino acids

MeSH Terms

Amino Acids
Amino Acids, Branched-Chain
Animal Experimentation
Animal Testing Alternatives
Animals
Ethics
Japan
Korea
Liver
Metabolic Diseases
Metabolomics*
Mice*
Models, Animal
Pathology, Clinical
Physiology
Streptozocin
Amino Acids
Amino Acids, Branched-Chain
Streptozocin

Figure

• 

  Figure 1 Changes in (A) body weight, (B) water and (C) food consumption after final administration of streptozotocin. Mice were given daily intraperitoneal injection with vehicle or 50 mg/kg body weight of streptozotocin (STZ) for 5 days. Changes were measured at least once a week after last dosing of streptozotocin during 4 weeks.

• 

  Figure 2 Changes of (A) serum glucose level, and relative ratio of (B) liver-to-body and (C) kidney-to-body weight in streptozotocin-treated mice. Mice were given daily intraperitoneal injection with vehicle or 50 mg/kg body weight of streptozotocin (STZ) for 5 days. Changes were examined 4 weeks after final administration. ***Significantly different from the corresponding vehicle-treated mice (ANOVA followed by Newman-Keuls multiple range test, P<0.001, respectively).

• 

  Figure 3 Effect of streptozotocin on the activities of (A) ALT and (B) AST. Mice were given daily intraperitoneal injection with vehicle or 50 mg/kg body weight of streptozotocin (STZ) for 5 days. Activities of ALT and AST were examined 4 weeks after final administration. *,**Significantly different from the corresponding vehicle-treated mice (ANOVA followed by Newman-Keuls multiple range test, P<0.05, 0.01, respectively).

• 

  Figure 4 Changes in (A) total cholesterol, (B) HDL-cholesterol, and (C) LDL-cholesterol in streptozotocin-treated mice. Mice were given daily intraperitoneal injection with vehicle or 50 mg/kg body weight of streptozotocin (STZ) for 5 days. Changes were examined 4 weeks after final administration. *Significantly different from the corresponding vehicle-treated mice (ANOVA followed by Newman-Keuls multiple range test, P<0.05, respectively).

• 

  Figure 5 Heat map of changes in serum metabolites between vehicle- and streptozotocin (STZ)-treated mice. Mice were given daily intraperitoneal injection with vehicle or 50 mg/kg body weight of streptozotocin (STZ) for 5 days. Serum metabolites were determined 4 weeks after final administration. Each column represents one mouse sample and each row represents a different metabolite.

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