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OACSTPCD

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.