Improvement of diabetes, obesity and hypertension in type 2 diabetic KKAy mice by bis(allixinato)oxovanadium(IV) complex.
Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx)(2)) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx)(2) was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx)(2) was examined in obesity-linked type 2 diabetic KKA(y) mice. Treatment of VO(alx)(2) for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA(y) mice; however, it had no effect on hypoadiponectinemia. VO(alx)(2) also improved hyperleptinemia, following attenuation of obesity in KKA(y) mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx)(2) is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.
Adachi
Yusuke
Y
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Yoshikawa
Yutaka
Y
Yoshida
Jiro
J
Kodera
Yukihiro
Y
Katoh
Akira
A
Takada
Jitsuya
J
Sakurai
Hiromu
H
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006973:Hypertension / Q000188:drug therapy*; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008956:Models, Chemical; D009765:Obesity / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000494:pharmacology*; D014018:Tissue Distribution
D020738:Leptin; D009942:Organometallic Compounds; C511635:bis(allixinato)oxovanadium(IV)