Development of a novel antidiabetic drug based on the targeting of GnT-IVa glycosyltransferase

我们专注于糖基转移酶“GnT-IVa”的生理和功能调节机制，调节胰腺β细胞的葡萄糖传感器功能，以开发一种新的抗糖尿病药物。我们已经发现，高脂肪饮食诱导胰腺细胞显著的氧化应激，这可能是抑制GnT-IVa表达的触发因素，并在2型糖尿病的发病机制中减少葡萄糖刺激的胰岛素分泌。此外，我们在体内工程表达了GnT-IVa在胰腺β细胞中，发现它们对高脂肪饮食诱导的糖尿病具有抵抗性，这强烈表明GnT-IVa是开发降糖药物的重要靶点。我们建立了基于细胞的检测系统，从化学文库中寻找增强GnT-IVa表达的药物化合物。

We have focused on the physiological and functional regulation mechanism of a glycosyltransferase "GnT-IVa", modulating the glucose sensor function of pancreatic beta cells, for developing a novel antidiabetic drug. We have revealed that high fat-diet induces significant oxidative stress in pancreatic beta cells that can be a trigger to suppress GnT-IVa expression and diminishes glucose stimulated insulin secretion in the pathogenesis of type 2 diabetes. Besides, we engineered to express GnT-IVa in pancreatic beta cells in vivo, and then revealed that they are resistant to the high fat-diet induced diabetes that strongly suggest that GnT-IVa is an important target to develop antidiabetic drugs. We established cell-based assay system for exploring the drug compounds enhancing GnT-IVa expression from chemical libraries.