5-HT promotes pancreatic α-to-β cell transdifferentiation. Journal Articles uri icon

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abstract

  • The role of 5-HT in maintaining glucose homeostasis during metabolic stress and inhibiting glucagon secretion is well documented, however, its effect on α cell identity remained unclear. In this study, we demonstrated that 5-HT suppressed the expression of α cell markers, such as Arx and Gcg, while enhancing the expression of β cell markers in mouse pancreatic α cell lines. We further found that treatment with 5-HT significantly increased the percentage of Gcg+Ins+ and Gcg+Nkx6.1+ cells in isolated human and mouse islets. Using pancreatic α cell lineage-tracing Gcgcre+; tdTomato/tdTomato mice, we observed that 5-HT treatment significantly reduced random blood glucose levels and increased tdTomato+Ins+, Gcg+Ins+ and Gcg+Nkx6.1+ cells in a high fat diet and streptozotocin (HFD + STZ) induced diabetes model. Additionally, in situ detection of 5-HT production in the human pancreas revealed a reduction of 5-HT expression in β cells of human T2D patients. These findings suggest that 5-HT treatment induces the transdifferentiation of α to β cells, potentially contributing to the recovery of β cell mass in T2D.

authors

  • Liu, Na
  • Liu, Tengli
  • Alim, Nijat
  • Zou, Jiaqi
  • Hu, Xiaoyan
  • Zhang, Boya
  • Liu, Fei
  • Ding, Xuejie
  • Sun, Peng
  • Wang, Shusen
  • Zhang, Lanqiu
  • Zheng, Rongxiu
  • Liang, Rui

publication date

  • June 2025