| In the 21st century, patients suffering from diabetes mellitus(DM), a lifestyle-related disease, will increase more than 20th. DM is threatening to human health because of the development of many severe secondary complications. So diabetes research has never been so intense. Along with important improvement in the scientific tools and techniques, deep insights into the complex inter-relationship between insulin action, insulin resistance, lipid and carbohydrate metabolism have been made. Discovery was made in vivo and vitro demonstrating that vanadium can enhance and/or mimic the physiological effects of insulin in an experimental model of diabetes. After many trials, people noticed that vanadium might be very useful in the treatment of type 2 diabetes and metabolic syndrome because vanadium enhanced insulin sensitivity and improved insulin resistance. It is strongly desired that vanadium would be a new drug for diabetes treatment. The effect of vanadium in lowering blood glucose in diabetes animals is well established; however, the exact mechanism of action of vanadium still remains unknown. There are several reports from in vitro studies indicating that vanadium increases enzyme activity in insulin signaling pathway, such as it stimulates autophosphorylation of insulin receptors, increases insulin receptor tyrosine kinase activity, increases protein tyrosine kinase activity, increases Ser/Thr protein kinase activity and inhibits phosphotyrosine phosphatase activity, however, these findings have not been duplicated in vivo.We demonstrated that vanadium significantly ameliorated the disorder of glucose and lipid without increasing insulin secretion and markedly improved glucose uptake and utilization of skeletal muscles in our study before. Skeletal muscle is an important site for the uptake and utilization of glucose from the blood, it is rich in the vesicles containing the insulin dependent glucose transporter GLUT4. In the present study we have measured the in vivo effect of vanadium at the level of GLUT4 expression in skeletal muscle. To determine the relationship between the glucose lowering effects of vanadium on GLUT4 expression, it was found that plasma glucose, triglyceride and insulin levels were significantly lower in the diabetes-treated group, (DV) after 4 weeks treatment. Densitometric measurement showed a decrease of 35%and 50%. GLUT4 and GLUT4 mRNA respectively in the total membrane fraction of the skeletal muscle of STZ-diabetic rats(D) as compared to untreated control(C). GLUT4 and GLUT4 mRNA level were restored to control levels after 4 weeks treatment. It showed that vanadium can increase GLUT4 expression in skeletal musele of diabetic animals. Whether this occurs through a direct interaction with GLUT4 promoter or through a yet unknown pathway remains to be elucidated. And it may at least partially explain the glucoregulatory effects of vanadium.We also studied that the effect of vanadium treatment on insulin stimulated GLUT4 translocation and GLUT4/ GLUT4 mRNA expression in cardiac tissue of STZ-D rats. Densitometic measurement showed a decrease of 52%, 62% GLUT4 and GLUT4 mRNA in the total membrane fraction of the cardiac tissue of STZ-D rats(D) as compared to untreated control(C). GLUT4 and GLUT4 mRNA were restored to control level after 4 weeks vanadium treatment. But GLUT4 (53%) level of sarcolemmal membrane were not restored in DV group as compared to C group. At 5 min after insulin injection, sarcolemmal membrane GLUT4 level was significantly increased in DV+I group as compared to DV group.It suggests that vanadium can increase GLUT4 protein and gene expression and enhances insulin-mediated GLUT4 translocation in cardiac tissue by enhancing its early response.To investigate the effects of vanadate on β-cell function, in this study, isolated human embryo pancreatic islet cells were cultured at 0.1mM(low) and 0.5mM(high) concentrations of vanadium. The study indicates that LV can increase pancreatic islet cells grow very well, and enhance insulin secretion. HV has a...
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