Li Changhong, Zhang Yi, Chen Li, Li Xiaoying
Nanjing AscendRare and Hua Medicine, Nanjing, Jiangsu 210000, China.
Hua Medicine, Shanghai 201203, China.
Life Metab. 2023 Jul 13;2(5):load031. doi: 10.1093/lifemeta/load031. eCollection 2023 Oct.
Glucokinase (GK) plays a pivotal role in glucose homeostasis as the glucose sensor in the pancreas and liver. Loss of function of GK results in hyperglycemia, and gain of function causes congenital hyperinsulinemic hypoglycemia. We speculate that the progressive loss of GK at both messenger RNA (mRNA) and protein levels in the islets and liver would be the key mechanism for Type 2 diabetes (T2D) pathogenesis. The development of GK activator (GKA) as an anti-diabetic drug has been endeavored for several decades. The failure of the early development of GKAs is due to the limitation of understanding the mode of GKA action. The success of dorzagliatin in the treatment of T2D has brought new hope for GK in setting a good model for repairing the underlying defects in the pancreatic islets and liver of T2D patients.
葡萄糖激酶（GK）作为胰腺和肝脏中的葡萄糖传感器，在葡萄糖稳态中起着关键作用。GK功能丧失会导致高血糖，而功能增强则会导致先天性高胰岛素血症性低血糖。我们推测，胰岛和肝脏中GK在信使核糖核酸（mRNA）和蛋白质水平上的逐渐丧失将是2型糖尿病（T2D）发病机制的关键机制。几十年来，人们一直在努力开发作为抗糖尿病药物的GK激活剂（GKA）。早期GKA开发的失败是由于对GKA作用模式的理解有限。多扎格列艾汀治疗T2D的成功为GK带来了新的希望，为修复T2D患者胰岛和肝脏的潜在缺陷树立了良好的典范。
