Transcriptional control of pancreatic β-cell identity and plasticity during the pathogenesis of type 2 diabetes

Type 2 diabetes (T2D) is caused by insulin resistance and insufficient insulin secretion. Evidence has increasingly indicated that pancreatic beta-cell dysfunction is the primary determinant of T2D disease progression and remission. High plasticity is an important feature of pancreatic beta-cells. During T2D development, pancreatic beta-cells undergo dynamic adaptation. Although beta-cell death/apoptosis in later-stage T2D is the major cause of beta-cell dysfunction, recent studies have revealed that beta-cell dedifferentiation and reprogramming, which play critical roles in beta-cell functional regulation in the early and middle T2D progression stages, are characterized by (i) a loss of mature beta-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 beta-cell identity during pancreatic development have been extensively studied. Here, we summarize the roles and underlying mechanisms of TFs in the maintenance of beta-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 beta-cell identity and plasticity will pave the way for developing more effective strategies, such as beta-cell regeneration therapy, to treat T2D and associated metabolic disorders. Copyright (C) 2022, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.

Automated summary

Type 2 diabetes (T2D) is a disease caused by insulin resistance and insufficient insulin secretion. Pancreatic beta-cell dysfunction is the primary determinant of T2D progression and remission. Recent studies have shown that beta-cell dedifferentiation and reprogramming play important roles in the early and middle stages of T2D progression. Understanding the transcriptional control of beta-cell identity and plasticity can lead to the development of more effective strategies for treating T2D.