（1. 山东中医药大学第一临床医学院，济南 250014；2. 北京中医药大学中医学院，北京 102488；3. 潍坊市中医院，潍坊 261000；4. 北京中医医院延庆医院，北京 102100；5. 山东中医药大学附属医院，济南 250011）
摘　要：胰岛β细胞是人体唯一合成并分泌胰岛素的细胞，对血糖稳态的调节至关重要。无氧糖酵解压力持续增加引发胰岛β细胞失代偿是导致2型糖尿病（T2DM）患者胰岛素分泌缺陷或胰岛素抵抗的重要原因之一。葡萄糖激酶（GK）作为葡萄糖传输的主要限速步骤，与胰岛素分泌密切相关。缺氧诱导因子1α亚基（HIF-1α）和6-磷酸果糖-2-激酶（PFKFB3）是糖酵解的关键调节因子，HIF-1α/PFKFB3信号通路参与调节胰岛β细胞复杂的病理生理过程，调节高糖环境下胰岛β细胞的稳态。本文探讨了HIF-1α/PFKFB3信号通路介导的GK如何通过厌氧糖酵解、线粒体网络断裂、氧化应激和去分化诱导等过程导致T2DM中胰岛β细胞发生功能障碍。这一研究能为临床防治T2DM提供新的思路。
关键词：2型糖尿病；葡萄糖激酶；HIF-1α/PFKFB3信号通路；线粒体；去分化
中图分类号：R587.1                           文献标志码：ADOI：10.3969/j.issn.1007-7146.2024.06.005

(1. The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China; 2. College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China; 3. Weifang Hospital of Traditional Chinese Medicine, Weifang 261000, China; 4. Yanqing Hospital of Beijing Chinese Medicine Hospital, Beijing 102100, China; 5. Affiliated Hospital of Shandong University of Chinese Medicine, Jinan 250011, China)
Abstract: Islet β cells are the exclusive cellular source of insulin synthesis and secretion, playing a crucial role in regulating blood glucose homeostasis. The impairment of islet β cells due to sustained anaerobic glycolysis pressure represents a significant factor contributing to insulin deficiency or resistance in patients with type 2 diabetes mellitus (T2DM). Glucokinase (GK), serving as the principal rate-limiting step in glucose transport, exhibits close association with insulin secretion. Hypoxia-inducible factor 1α subunit (HIF-1α) and 6-phosphofructo-2-kinase (PFKFB3) act as pivotal regulatory factors within glycolysis. The HIF-1α/PFKFB3 signaling pathway participates in intricate pathophysiological processes involving islet β cell function and maintenance under high-glucose conditions. This review elucidates the mechanisms by which the HIF-1α/PFKFB3 signaling pathway mediates GK induction through anaerobic glycolysis, mitochondrial network adaptive fragmentation, oxidative stress, and dedifferentiation leading to pancreatic islet β cell dysfunction in T2DM, thereby offering novel insights for clinical prevention and treatment strategies targeting T2DM.
Key words: type 2 diabetes; glucokinase; HIF-1α/PFKFB3 signaling pathway; mitochondria; dedifferentiation
（Acta Laser Biology Sinica, 2024, 33(6): 512-522）