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

作　　者：Ziyin Zhang Yue Gao Zhuo-Xian Meng 

机构地区：[1]Department of Pathology and Pathophysiology and Department of Geriatrics of Affiliated Hangzhou First People’s Hospital,Zhejiang University School of Medicine,Hangzhou,China [2]Key Laboratory of Disease Proteomics of Zhejiang Province,Zhejiang University School of Medicine,Hangzhou,Zhejiang,310058,China [3]Department of Geriatrics,Affiliated Hangzhou First People’s Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,310006,China

出　　处：《Journal of Genetics and Genomics》2022年第4期316-328,共13页遗传学报（英文版）

基　　金：supported by grants from the Training Program of the Major Research Plan of the National Natural Science Foundation of China (91857110);the National Key Research and Development Programme of China (2018YFA0800403 and 2016YFC1305303);the National Natural Science Foundation of China (81670740);the National Natural Science Fund for Excellent Young Scholars of China (81722012);the Zhejiang Provincial Natural Science Foundation of China (LZ21H070001);the Innovative Institute of Basic Medical Sciences of Zhejiang University, and the Fundamental Research Funds for the Central Universities, the Construction Fund of Medical Key Disciplines of Hangzhou (No. OO20200055);the Hangzhou Science and Technology Bureau (20150733Q13 and ZD20200129);the support from K.C. Wong Education Foundation

摘　　要：Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin secretion.Evidence has increasingly indicated that pancreaticβ-cell dysfunction is the primary determinant of T2D disease progression and remission.High plasticity is an important feature of pancreaticβ-cells.During T2D development,pancreaticβ-cells undergo dynamic adaptation.Althoughβ-cell death/apoptosis in later-stage T2D is the major cause ofβ-cell dysfunction,recent studies have revealed thatβ-cell dedifferentiation and reprogramming,which play critical roles inβ-cell functional regulation in the early and middle T2D progression stages,are characterized by(i)a loss of matureβ-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 ofβ-cell identity during pancreatic development have been extensively studied.Here,we summarize the roles and underlying mechanisms of TFs in the maintenance ofβ-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 ofβ-cell identity and plasticity will pave the way for developing more effective strategies,such asβ-cell regeneration therapy,to treat T2D and associated metabolic disorders.

关 键 词：Type 2 diabetes Pancreaticβ-cell Transcription factors DEDIFFERENTIATION TRANSDIFFERENTIATION REDIFFERENTIATION 

分 类 号：R587.1[医药卫生—内分泌]