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Volume 49 Issue 4
Apr.  2022
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Article Navigation >  Journal of Genetics and Genomics  > 2022  >  49(4): 316-328

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

doi: 10.1016/j.jgg.2022.03.002
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    a Department of Pathology and Pathophysiology and Department of Geriatrics of Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China;

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    b Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China;

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    c Department of Geriatrics, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, China

Funds:

We apologize to the authors whose relevant findings were not cited and discussed here due to space limitation. This work was 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), and the support from K.C. Wong Education Foundation.

  • Received Date: 2021-12-08
  • Accepted Date: 2022-03-06
  • Rev Recd Date: 2022-02-23
  • Publish Date: 2022-04-30
    Abstract
  • 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 progression and remission. High plasticity is an important feature of pancreatic β-cells. During T2D development, 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 progression 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 extensively 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.
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