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 KKAy mice. Treatment of VO(alx)2 for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKAy mice; however, it had no effect on hypoadiponectinemia. VO(alx)2 also improved hyperleptinemia, following attenuation of obesity in KKAy 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