Xiang Xie, Shuya Pan, Jiamin Zhang, Zihan Zhang, Xumei Yang, Jingjin Liu
Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Childrens' Hospital of Wenzhou Medical University, Wenzhou, Zhejieng 325027, China.
Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Curr Diabetes Rev. 2025;21(4):47-56. doi: 10.2174/0115733998278669240226061329.
The role of 3-phosphoinositide-dependent kinase 1 (PDK1) has been welldocumented in the development of diabetes. This review offers a thorough examination of its composition and associated routes, specifically focusing on insulin signaling and glucose processing. By examining the precise connection between PDK1 and diabetes, various strategies specifically targeting PDK1 were also investigated. Additionally, recent discoveries from mouse models were compiled where PDK1 was knocked out in certain tissues, which demonstrated encouraging outcomes for focused treatments despite the absence of any currently approved clinical PDK1 activators. Moreover, the dual nature of PDK1 activation was discussed, encompassing both anti-diabetic and pro-oncogenic effects. Hence, the development of a PDK1 modifier is of utmost importance, as it can activate anti-diabetic pathways while inhibiting pro-oncogenic pathways, thus aiding in the treatment of diabetes. In general, PDK1 presents a noteworthy opportunity for future therapeutic strategies in the treatment of diabetes.
3-磷酸肌醇依赖性激酶1（PDK1）在糖尿病发展过程中的作用已有充分记载。本综述对其组成和相关途径进行了全面研究，特别关注胰岛素信号传导和葡萄糖代谢过程。通过研究PDK1与糖尿病之间的精确联系，还对各种特异性靶向PDK1的策略进行了调查。此外，整理了近期在某些组织中敲除PDK1的小鼠模型的研究发现，尽管目前尚无批准的临床PDK1激活剂，但这些研究结果为针对性治疗带来了令人鼓舞的成果。此外，还讨论了PDK1激活的双重性质，包括抗糖尿病和促癌作用。因此，开发一种PDK1调节剂至关重要，因为它可以激活抗糖尿病途径，同时抑制促癌途径，从而有助于糖尿病的治疗。总体而言，PDK1为未来糖尿病治疗策略提供了一个值得关注的契机。
