Validation of the Vps34 PI 3-kinase as a new potential drug target in insulin sensitization

本提案旨在验证Vps34酶在代谢中起作用的假设。在我们之前的研究中，我们在小鼠中使用遗传方法并由BBSRC资助，我们发现Vps34的部分失活可以改善葡萄糖耐量并防止高脂肪饮食的负面影响。这表明Vps34抑制剂可能对糖尿病等疾病有用。我们现在打算在基于细胞和小鼠的模型中测试新开发的Vps34化学阻滞剂是否能诱导与Vps34基因失活相同的效果。这是一个概念验证项目，如果结果是积极的，可以为Vps34药物开发和转化工作规划奠定基础。

This proposal aims to test the hypothesis that the Vps34 enzyme plays a role in metabolism. In our previous studies, using genetic approaches in the mouse and funded by the BBSRC, we have discovered that partial inactivation of Vps34 leads to improved glucose-tolerance and protection against the negative effects of a high fat diet. This suggests that Vps34 inhibitors could be useful in diseases such as diabetes. We now propose to test whether newly developed chemical blockers of Vps34 can induce the same effects as genetic inactivation of Vps34, in cell- and mouse-based models. This is a proof-of-concept project which, if the outcome is positive, can lay the foundations for Vps34 drug development and a translational programme of work.