HIF-1α/PFKFB3信号通路介导GK调节2型糖尿病胰岛β细胞功能的研究进展  

HIF-1α/PFKFB3 Signaling Pathway Mediates GK Regulation of Islets in Type 2 Diabetes β Progress in Cellular Function Research

作　　者：魏皓月 张茜 魏代浩 李欢 王瑞 黄延芹[5] WEI Haoyue;ZHANG Xi;WEI Daihao;LI Huan;WANG Rui;HUANG Yanqin(The First Clinical Medical College,Shandong University of Traditional Chinese Medicine,Jinan 250014,China;College of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;Weifang Hospital of Traditional Chinese Medicine,Weifang 261000,China;Yanqing Hospital of Beijing Chinese Medicine Hospital,Beijing 102100,China;Affiliated Hospital of Shandong University of Chinese Medicine,Jinan 250011,China)

机构地区：[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

出　　处：《激光生物学报》2024年第6期512-522,共11页Acta Laser Biology Sinica

基　　金：国家自然科学基金项目(81974562);山东省泰山学者工程专项项目(tsqn202211354);山东省自然科学基金项目(ZR2024MH245);钱秋海全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号)。

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。Isletβcells are the exclusive cellular source of insulin synthesis and secretion,playing a crucial role in regulating blood glucose homeostasis.The impairment of isletβcells 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 1αsubunit(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 isletβcell 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 isletβcell dysfunction in T2DM,thereby offering novel insights for clinical prevention and treatment strategies targeting T2DM.

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 

分 类 号：R587.1[医药卫生—内分泌]