Type II diabetes affects approximately 310 million individuals worldwide, and its prevalence is rapidly increasing. The disease is normally preceded by insulin resistance that results from obesity. The excess storage of fat in extra-adipose tissues, especially cardiac and skeletal muscles, impairs the ability of cells to respond sufficiently to insulin, leading to elevated glucose levels in the blood. Few treatments for type II diabetes directly target this fat accumulation. Now, an international team of collaborators led by Ulf Erikkson (Karolinska Institute, Stockholm, Sweden), together with researchers at the University of Melbourne (Heidelberg, Australia) and at the drug company CSL, Ltd. (Parkville, Australia), have found that blocking the signaling of a protein called VEGF-B prevents fat from accumulating in muscles and in the heart so that the cells in these tissues are once again able to respond to insulin.

The researchers reported the results of four different studies of VEGF-B in (Nature published online 26 September 2012; doi:10.1038/nature11464). Two studies examined the effects of genetically deleting VEGF-B on diabetes development. Mice that genetically lacked the ability to produce VEGF-B were crossed with a strain of mice genetically prone to developing diabetes. The offspring produced from these crosses had normal blood glucose levels and decreased accumulation of fat in their muscles and heart. When VEGF-B was genetically deleted in mice that were fed a high-fat diet, the mice were similarly protected from developing diabetes despite gaining more weight. These findings suggest that VEGF-B is necessary in the development of type II diabetes.

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In another study, mice of the same diabetes-prone strain were treated with an antibody against VEGF-B for 10 weeks, either preventatively (given to pre-diabetic mice) or therapeutically (given to diabetic mice). Treatment of pre-diabetic mice with the drug prevented the development of insulin resistance as well as storage of lipids in muscle and heart tissues. Treatment of the diabetic mice was also effective; the drug halted the progression of the disease. A final study applied the drug treatment to a group of rats fed a high-fat diet for 8 weeks and given the drug in parallel. The treatment restored insulin sensitivity, increased muscle glucose usage and reversed diabetes pathology in the rats.

Said coauthor Ake Sjoholm in a press release, “The results we present in this study represent a major breakthrough and an entirely new principle for the prevention and treatment of type II diabetes.”