Switching from singlet-oxygen-mediated oxidation to free-radical-mediated oxidation in the pathogenesis of type 2 diabetes in model mouse.
Oxidative stress plays a key role in the development of type 2 diabetes. However, it is still unknown what kind of oxidative stress underlies the development of type 2 diabetes. We investigated hydroxyoctadecadienoic acid (HODE) isomers, which have been proposed as a biomarker for evaluating oxidative stress in vivo, during the development of diabetes in Tsumura Suzuki Obese Diabetes (TSOD) mouse, a type 2 diabetes model. It was revealed that glucose tolerance and insulin resistance index HOMA-IR in TSOD mice at 5 weeks of age were approximately normal, namely, the mice were in the prediabetic state, but these levels were significantly exacerbated from 8 weeks of age compared with those in Tsumura Suzuki Non Obesity (TSNO) mice (control). Concomitantly, the plasma levels of free-radical-mediated oxidation products, 9- and 13-(E,E)-HODE and 7β-hydroxycholesterol, in TSOD mice were significantly higher than those in TSNO mice at 8, and 8 and 11 weeks of age, respectively. Interestingly, the plasma levels of 10- and 12-(Z,E)-HODE, which are produced specifically by singlet-oxygen-mediated oxidation, in TSOD mice were higher than those in TSNO mice only at 5 weeks of age, and not at 8, 11, and 13 weeks of age. We demonstrated that singlet-oxygen-mediated oxidation occurred in TSOD mice before development of the diabetic phenotypes, including impaired glucose tolerance and insulin resistance. These results suggest that excessive singlet-oxygen-mediated oxidation plays an important role in the pathogenesis of type 2 diabetes.
Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) , Takamatsu, Kagawa , Japan.
K
K
Murotomi
A
A
Umeno
M
M
Yasunaga
M
M
Shichiri
N
N
Ishida
H
H
Abe
Y
Y
Yoshida
Y
Y
Nakajima
D000818:Animals; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004195:Disease Models, Animal; D005609:Free Radicals / Q000737:chemistry; D018149:Glucose Intolerance / Q000209:etiology*; D007333:Insulin Resistance; D008041:Linoleic Acids / Q000097:blood; D044243:Linoleic Acids, Conjugated / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008820:Mice, Obese; D018384:Oxidative Stress; D026082:Singlet Oxygen / Q000737:chemistry*
D015415:Biomarkers; D005609:Free Radicals; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C075806:8-hydroxylinoleic acid; C024347:9-hydroxy-10,12-octadecadienoic acid; D026082:Singlet Oxygen; C024348:13-hydroxy-9,11-octadecadienoic acid
TSOD mouse; free radical; oxidative stress; singlet oxygen; type 2 diabetes