Role of vanadyl acetylacetonate-induced elevation of reactive oxygen species in the regulation of lipolysis and glucose metabolism in 3T3L1 adipocytes
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© 2015 Journal of Chinese Pharmaceutical Sciences. In the present study, we investigated the role of reactive oxygen species (ROS) elevation induced by an anti-diabetic vanadium compound, vanadyl acetylacetonate (VO(acac)2), in the regulation of lipolysis and glucose metabolism using differentiated 3T3L1 adipocytes as a model system. By confocal laser scanning microscopy, we found that VO(acac)2 induced ROS generation under high glucose stimulation, and the pretreatment of NADPH oxidase inhibitors could significantly reduce the elevated ROS level. Meanwhile, the decreased phosphorylated levels of AKT and the two key modulators of lipolysis (HSL and perilipin) were observed by western blot analysis. We also found that the contents of glycerol release were further reduced as well. In addition, the levels of key regulatory proteins, AS160 and GSK3ß, in glucose metabolism pathway were correspondingly reduced. These findings demonstrated that ROS induced by vanadium compounds could act as a metabolic signal to activate AKT pathway to inhibit lipolysis and promote glucose transport and glycogen synthesis rather than by direct action by themselves. Our study contributed to elucidate the anti-diabetic effects of vanadium compounds and provided a theoretical basis for the further development of new vanadium complexes in the prevention and therapeutics of diabetes.
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