| First Author | Sun Y | Year | 2021 |
| Journal | Cell Rep | Volume | 34 |
| Issue | 1 | Pages | 108576 |
| PubMed ID | 33406428 | Mgi Jnum | J:304295 |
| Mgi Id | MGI:6694797 | Doi | 10.1016/j.celrep.2020.108576 |
| Citation | Sun Y, et al. (2021) Expression of miRNA-29 in Pancreatic beta Cells Promotes Inflammation and Diabetes via TRAF3. Cell Rep 34(1):108576 |
| abstractText | Type 2 diabetes mellitus (T2DM) is recognized as a chronic, low-grade inflammatory disease characterized by insulin resistance and pancreatic beta cell dysfunction; however, the underlying molecular mechanism remains unclear. Here, we report a key beta cell-macrophage crosstalk pathway mediated by the miRNA-29-TNF-receptor-associated factor 3 (TRAF3) axis. beta 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 beta 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 beta cells to modulate the systemic inflammatory tone and glucose homeostasis via miR-29 in response to nutrient overload. |
