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

摘要

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.