Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as dr...Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis（acetylacetonato）-oxidovanadium（Ⅳ）（VO（acac）_2） could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO（acac）_2 were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO（acac）_2 might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.展开更多
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 gluc...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 GSK3β, 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.展开更多
基金supported by National Natural Science Foundation of China(Grant No.21171011 and 21671009)
文摘Insulin resistance is characterized as one of crucial pathological changes in type 2 diabetes mellitus（T2DM）, and dyslipidaemia is frequently detected in T2DM. A variety of vanadium compounds have been studied as drug candidates for diabetes based on their insulin-like action. However, few studies focus on their antilipolytic effect. In the present study, we established an insulin-resistant model in 3T3-L1 adipocytes to mimic pathological conditions of T2DM according to a well-established method by the treatment of high concentrations of glucose and insulin, which was validated by oil red O staining and the decreased levels of phosphorylated Akt, AS160 and GSK3 after insulin treatment. The results demonstrated that bis（acetylacetonato）-oxidovanadium（Ⅳ）（VO（acac）_2） could inhibit isoproterenol-stimulated lipolysis through the reduction of the phosphorylated HSL and perilipin levels in both insulin-sensitive and insulin-resistant 3T3-L1 adipocytes. Moreover, although the levels of phosphorylated Akt induced by VO（acac）_2 were decreased, the rates of lipolytic inhibition were not significantly altered compared with those under insulin-sensitive condition, indicating that the anti-lipolytic effect of VO（acac）_2 might also function in an Akt-independent way in insulin-resistant adipocytes. Our work here help elucidate the anti-diabetic effects of vanadium compounds. It may not only shed light on the utility of vanadium-based compounds as potential anti-diabetic drugs but also serve as a useful screening model for new anti-diabetic drugs.
基金National Natural Science Foundation of China(Grant No.20871008 and 21171011)
文摘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 GSK3β, 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.
