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

血管内皮在血糖代谢中的作用研究

• 批准号: 226258562
• 负责人: Professor Dr. Eckhard Lammert
• 金额: --
• 依托单位: Institut für Stoffwechselphysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/226258562?language=en
• 关键词: Investigation; role; blood; vessel; endothelium

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.

血管内皮细胞与胰腺β细胞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。在之前的资助期内，我们发现了血管内皮生长因子（VEGF-A）拮抗剂Semaphorin-3A （Sema3A）可以调节小鼠的血糖水平，这是一个尚未报道的新发现。我们的数据强烈表明，Sema3A与人类2型糖尿病（T2DM）存在遗传关联，目前全球有超过2.5亿人患有这种疾病。此外，我们发现Sema3A在T2DM患者的胰岛以及高脂肪饮食的高血糖小鼠的几个组织中的表达增加。我们还可以证明，Sema3A的缺失改善了小鼠的血糖水平和葡萄糖耐量，这表明Sema3A可能成为治疗人类2型糖尿病（T2DM）的药物靶点。项目更新的目标是表征Sema3A调节血糖水平的内皮细胞机制。