葡萄糖-6-磷酸酶催化亚基 (G6PC)1 和 G6PC2 对于葡萄糖代谢至关重要，调节糖酵解、糖异生和糖原分解等过程。尽管结构和功能相似，G6PC1 和 G6PC2 却表现出不同的组织特异性表达模式、G6P 水解动力学和生理功能。这篇综述全面概述了它们的酶学和在葡萄糖稳态中的独特作用。我们研究了 G6PC1 失活突变如何导致糖原贮积病，以及 G6PC1 和 G6PC2 表达升高如何影响糖尿病并发症的发生率、2 型糖尿病 (T2DM) 和各种癌症的风险。我们还讨论了抑制 G6PC1 和 G6PC2 以防止血糖水平升高引起的并发症的潜力，并重点介绍了针对 G6PC1 和 G6PC2 的药物开发工作，以及抑制剂用于疾病预防的治疗潜力。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Glucose-6-phosphatase catalytic subunit (G6PC)1 and G6PC2 are crucial for glucose metabolism, regulating processes like glycolysis, gluconeogenesis, and glycogenolysis. Despite their structural and functional similarities, G6PC1 and G6PC2 exhibit distinct tissue-specific expression patterns, G6P hydrolysis kinetics, and physiological functions. This review provides a comprehensive overview of their enzymology and distinct roles in glucose homeostasis. We examine how inactivating mutations in G6PC1 lead to glycogen storage disease, and how elevated G6PC1 and G6PC2 expression can affect the incidence of diabetic complications, risk for type 2 diabetes mellitus (T2DM) and various cancers. We also discuss the potential of inhibiting G6PC1 and G6PC2 to protect against complications from elevated blood glucose levels, and highlight drug development efforts targeting G6PC1 and G6PC2, and the therapeutic potential of inhibitors for disease prevention.Copyright © 2024 Elsevier Ltd. All rights reserved.