摘要Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin secretion.Evidence has increasingly indicated that pancreatic β-cell dysfunction is the primary determinant of T2D disease pro-gression and remission.High plasticity is an important feature of pancreaticβ-cells.During T2D develop-ment,pancreatic β-cells undergo dynamic adaptation.Although β-cell death/apoptosis in later-stage T2D is the major cause of β-cell dysfunction,recent studies have revealed that β-cell dedifferentiation and reprogramming,which play critical roles in β-cell functional regulation in the early and middle T2D pro-gression stages,are characterized by(ⅰ)a loss of mature β-cell-enriched genes;(ⅱ)dedifferentiation to a progenitor-like state;and(ⅲ)transdifferentiation into other cell types.The roles of transcription factors(TFs)in the establishment and maintenance of β-cell identity during pancreatic development have been exten-sively studied.Here,we summarize the roles and underlying mechanisms of TFs in the maintenance of β-cell identity under physiological and type 2 diabetic conditions.Several feasible approaches for restoring islet functions are also discussed.A better understanding of the transcriptional control of β-cell identity and plasticity will pave the way for developing more effective strategies,such as β-cell regeneration therapy,to treat T2D and associated metabolic disorders.