Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3

Cell Rep. 2021 Jan 5;34(1):108576. doi: 10.1016/j.celrep.2020.108576.


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.

Keywords: TRAF3; chronic inflammation; exosome; glucose metabolism; insulin resistance; metabolic stress; miR-29; monocytes and macrophages; type 2 diabetes mellitus; β cell dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diet, High-Fat
  • Exosomes / metabolism
  • Glucose / metabolism
  • Glucose Intolerance / metabolism
  • Humans
  • Inflammation / metabolism*
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / metabolism*
  • Rats
  • Rats, Wistar
  • Signal Transduction*
  • TNF Receptor-Associated Factor 3 / metabolism*


  • Insulin
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • TNF Receptor-Associated Factor 3
  • Glucose