Role of copper ion in the pathogenesis of type 2 diabetes.
Reactive oxygen species (ROS) are induced under diabetic conditions and are likely associated with the development of type 2 diabetes. It is also known that ROS production is facilitated in the presence of copper ion through the Fenton reaction. The aim of this study was to examine the involvement of copper ion in the pathogenesis of type 2 diabetes and to evaluate the potential usefulness of a copper chelating agent for the treatment of type 2 diabetes. First, both serum copper ion and ROS levels in diabetic C57BL/KsJ-db/db mice were significantly higher compared to those in nondiabetic mice. Second, we treated diabetic db/db mice with a copper chelating agent tetrathiomolybdate and examined the effects on the development of type 2 diabetes. As the results, both serum copper ion and ROS levels were significantly decreased by the treatment, which were equivalent to those in non-diabetic mice. Consequently, the treatment with a copper chelating agent reduced insulin resistance and ameliorated glucose intolerance in diabetic db/db mice. In addition, serum triglyceride levels were also decreased by the treatment. In conclusion, our present results suggest that copper ion is involved in the development of type 2 diabetes and thereby a potential therapeutic target for diabetes.
Tanaka
Ayako
A
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Kaneto
Hideaki
H
Miyatsuka
Takeshi
T
Yamamoto
Kaoru
K
Yoshiuchi
Kazutomi
K
Yamasaki
Yoshimitsu
Y
Shimomura
Iichiro
I
Matsuoka
Taka-Aki
TA
Matsuhisa
Munehide
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002614:Chelating Agents / Q000627:therapeutic use; D003300:Copper / Q000097:blood / Q000633:toxicity*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008982:Molybdenum / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000097:blood
D001786:Blood Glucose; D002614:Chelating Agents; D017382:Reactive Oxygen Species; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate