Endocrine Connections (May 2022)

Txnip deficiency promotes β-cell proliferation in the HFD-induced obesity mouse model

  • Zhandong Lei,
  • Yunfei Chen,
  • Jin Wang,
  • Yan Zhang,
  • Wenjuan Shi,
  • Xuejiao Wang,
  • Dehai Xing,
  • Dongxue Li,
  • Xiangying Jiao

DOI
https://doi.org/10.1530/EC-21-0641
Journal volume & issue
Vol. 11, no. 4
pp. 1 – 15

Abstract

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Elucidating the mechanisms of regulation of β-cell proliferation is key to understanding the pathogenesis of diabetes mellitus. Txnip is a tumor suppressor that is upregulated in diabetes and plays an important role in the regulation of insulin sensitivity; however, its potential effect on pancreatic β-cell proliferation remains unclear. Here, we evaluated the role of Txnip in pancreatic β-cell compensatory proliferation by subjecting WT and Txnip knockout (KO) mice to a high-fat diet (HFD). Our results demonstrate that Txnip deficiency improves glucose tolerance and increases insulin sens itivity in HFD-induced obesity. The antidiabetogenic effect of Txnip deficiency was accompanied by increased β-cell proliferation and enhanced β-cell mass expansion. Furthermore, Txnip deficiency modulated the expression of a set of transcription factors with key roles in β-cell proliferation and cell cycle regulation. Txnip KO in HFD mice also led to activated levels of p-PI3K, p-AKT, p-mTOR and p-GSK3β, suggesting that Txnip may act via PI3K/AKT signaling to suppress β-cell proliferation. Thus, our work provides a theoretical basis for Txnip as a new therapeutic target for the treatment of diabetes mellitus.

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