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

血管内皮细胞和胰腺β细胞之间的相互作用及其在血糖调节中的作用已被研究，并发表了多篇论文。在之前的资助期间，我们发现Semaphorin-3A（Sema 3A），一种建议的血管内皮生长因子（VEGF-A）拮抗剂，调节小鼠的血糖水平-这是一项新的尚未报道的发现。我们的数据有力地表明，Sema 3A与人类2型糖尿病（T2 DM）有遗传相关性，该疾病目前影响全球超过2.5亿人。此外，我们发现，Sema 3A的表达增加，在胰岛的T2 DM患者以及在几个组织中的高血糖小鼠保持高脂肪饮食。我们还可以证明，删除Sema 3A改善小鼠的血糖水平和葡萄糖耐量，这表明Sema 3A可能成为治疗人类2型糖尿病（T2 DM）的药物靶标。项目更新的目标是表征Sema 3A调节血糖水平的基于内皮细胞的机制。

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.