Al-Hasani Hadi, Tschöp Matthias H, Cushman Samuel W
Department of Pharmacology, German Institute of Human Nutrition, 14558 Potsdam-Rehbrücke, Germany.
Mol Interv. 2003 Oct;3(7):367-70. doi: 10.1124/mi.3.7.367.
The hormones glucagon and insulin delicately regulate the concentration of blood glucose. When patients become resistant to the effects of insulin or produce too little of it to properly regulate glucose concentrations, then diabetes can result. Unfortunately, not all patients with insulin-resistant, type 2 diabetes mellitus respond to drugs that improve insulin sensitivity. However, there is reason to be hopeful. A new molecule that targets glucokinase (GK), the enzyme responsible for phosphorylating glucose in pancreatic beta cells and hepatic cells, acts to significantly reduce blood glucose concentrations in rodents. The GK activator RO-28-1675 increased the glucose affinity and Vmax of GK, and rats treated with RO-28-1675 had improved glucose tolerance and elevated glucose uptake in liver. These results provide the basis for improved drug design that may alleviate diabetes mellitus and the disorders that accompany it in patients.
胰高血糖素和胰岛素这两种激素精细地调节着血糖浓度。当患者对胰岛素的作用产生抗性，或者分泌的胰岛素过少而无法正常调节血糖浓度时，就可能引发糖尿病。不幸的是，并非所有胰岛素抵抗的2型糖尿病患者都对提高胰岛素敏感性的药物有反应。然而，仍有理由抱有希望。一种靶向葡萄糖激酶（GK）的新分子，该酶负责在胰腺β细胞和肝细胞中磷酸化葡萄糖，它能显著降低啮齿动物的血糖浓度。GK激活剂RO - 28 - 1675提高了GK的葡萄糖亲和力和最大反应速度（Vmax），用RO - 28 - 1675治疗的大鼠葡萄糖耐量得到改善，肝脏中的葡萄糖摄取增加。这些结果为改进药物设计提供了依据，有望缓解糖尿病患者及其伴随的病症。
