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VEGF-B Blockade in Muscle Endothelium:A Potential Barrier to Type 2 Diabetes

Obesity and increased lipid deposition in ectopic tissues, such as the heart and skeletal muscle, are linked to insulin insensitivity and type 2 diabetes. Vascular endothelial growth factor B (VEGF-B) is expressed in highly metabolic tissues and acts through endothelial receptors on skeletal and cardiac muscle to increase fatty acid uptake and lipid deposition. Mice lacking Vegfb exhibit lower fatty acid uptake and lipid deposition in muscle, suggesting that VEGF-B blockade at the level of the endothelium could be a novel treatment for type 2 diabetes. In a recent study, Hagberg et al. utilized murine models of diabetes (mice and rats on a high-fat diet [HFD] and diabetic db/db mice) to block VEGF-B action in both skeletal and cardiac muscle endothelia. In these experiments, genetic (deletion of the Vegfb gene) and pharmacologic (neutralizing anti–VEGF-B antibody) approaches were used. Vegfb knockout HFD and db/db mice exhibited decreased blood glucose levels and were more glucose tolerant compared with controls. In addition, Vegfb knockout db/db mice exhibited decreased lipid deposition and increased glucose uptake in skeletal and cardiac muscle compared with their wild-type counterparts. With respect to hyperglycemia, pharmacologic intervention with an anti–VEGF-B antibody was effective as both a preventive treatment in prediabetic db/db mice as well as a therapeutic agent in diabetic db/db mice. The anti–VEGF-B antibody also resulted in decreased lipid deposition in peripheral tissues and improved glucose tolerance in db/db mice relative to controls. The authors also investigated the effect of anti–VEGF-B antibody on insulin resistance and type 2 diabetes using HFD rats. VEGF-B blockade resulted in increased glucose infusion and disposal rates and increased glucose uptake in both skeletal and cardiac muscle. Based on results from both mice and rats, data from Hagberg’s laboratory suggest that prevention of VEGF-B activity could maintain pancreatic islet function and improve insulin resistance. …

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  1. doi: 10.2337/db12-dd01 Diabetes vol. 62 no. 1 311-312
  1. Free via Open Access: OA