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Title: Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3. Author: Sun Y, Zhou Y, Shi Y, Zhang Y, Liu K, Liang R, Sun P, Chang X, Tang W, Zhang Y, Li J, Wang S, Zhu Y, Han X. Journal: Cell Rep; 2021 Jan 05; 34(1):108576. PubMed ID: 33406428. 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.[Abstract] [Full Text] [Related] [New Search]