Investigation of the role of blood vessel endothelium in blood glucose metabolism

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The interaction between vascular endothelial cells and pancreatic beta cells and its role in blood glucose regulation have been investigated, and several papers were published. In the previous funding period we discovered that Semaphorin-3A (Sema3A), a suggested vascular endothelial growth factor (VEGF-A) antagonist, regulates blood glucose levels in mice - a novel and not yet reported finding. Our data strongly suggest that Sema3A is genetically associated with human Type 2 Diabetes Mellitus (T2DM), a disease currently affecting more than 250 million people worldwide. In addition, we showed that the expression of Sema3A was increased in pancreatic islets of T2DM patients as well as in several tissues in hyperglycemic mice kept on a high fat diet. We could also demonstrate that deletion of Sema3A improved blood glucose levels and glucose tolerance in mice, suggesting that Sema3A might become a drug target for human Type 2 Diabetes Mellitus (T2DM) treatment. The goal of the project renewal is to characterize the endothelial cell-based mechanism by which Sema3A regulates blood glucose levels.