Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3 Academic Article uri icon

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abstract

  • Type 2 diabetes mellitus (T2DM) is recognized as a chronic, low-grade inflammatory disease characterized by insulin resistance and pancreatic β cell dysfunction; however, the underlying molecular mechanism remains unclear. Here, we report a key β cell-macrophage crosstalk pathway mediated by the miRNA-29-TNF-receptor-associated factor 3 (TRAF3) axis. β cell-specific transgenic miR-29a/b/c mice are predisposed to develop glucose intolerance and insulin resistance when fed a high-fat diet (HFD). The metabolic effect of β cell miR-29 is largely mediated through macrophages because either depletion of macrophages or reconstitution with miR-29-signaling defective bone marrow improves metabolic parameters in the transgenic mice. Mechanistically, our data show that miR-29 promotes the recruitment and activation of circulating monocytes and macrophages and, hence, inflammation, via miR-29 exosomes in a TRAF3-dependent manner. Our results demonstrate the ability of β cells to modulate the systemic inflammatory tone and glucose homeostasis via miR-29 in response to nutrient overload.

authors

  • Sun, Yi
  • Zhou, Yuncai
  • Shi, Ying
  • Zhang, Yan
  • Liu, Kerong
  • Liang, Rui
  • Sun, Peng
  • Chang, Xiaoai
  • Tang, Wei
  • Zhang, Yujing
  • Li, Jing
  • Wang, Shusen
  • Zhu, Yunxia
  • Han, Xiao

publication date

  • January 2021

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