Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age

Abstract

Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice.

Keywords: TSOD mouse; hyperglycemia; inflammation; oxidative stress; type 2 diabetes.

Fig. 1

Changes in body weight (a), plasma total cholesterol (b), and non-fasting blood glucose (c) in TSNO (white bar) and TSOD (black bar) mice. Plasma total cholesterol level in TSNO mice set to 1. Results are expressed as means ± SE (n = 3–6). Statistical analyses were carried out using ANOVA (Tukey’s post-hoc test). *p<0.05.

Fig. 2

OGTT in TSNO and TSOD mice. Glucose levels before (0 min) and after (15, 30, 60, and 120 min) oral glucose loading in TSNO (white circle) and TSOD (black circle) mice at 5 (a) and 11 (b) weeks of age. Results are expressed as means ± SE (5 weeks of age: n = 11–12; 11 weeks of age: n = 6 each). Statistical analyses were carried out using the unpaired t test. *Significant difference from TSNO mice (p<0.05).

Fig. 3

Changes in fasting plasma TNF-α (a) and IL-6 (b) levels in TSNO (white bar) and TSOD (black bar) mice. Results are expressed as means ± SE (n = 6 each). N.D. indicates not detected.

Fig. 4

Plasma lipid oxidation products in TSNO (white bar) and TSOD (black bar) mice. Plasma tHODE level in TSNO mice was set to 1. Results are expressed as means ± SE (5 weeks TSNO and TSOD: n = 5 each; 11 weeks TSNO: n = 6; 11 weeks TSOD: n = 3). Statistical analyses were carried out using the unpaired t test. *Significant difference from age-matched TSNO mice (p<0.05).