miR-101a and miR-30b contribute to inflammatory cytokine-mediated β-cell dysfunction

Inflammatory cytokines have a critical role in the progressive deterioration of pancreatic beta-cell function and development of type 1 diabetes. Prolonged exposure of beta-cells to inflammatory cytokines results in gene expression modifications, leading to loss of beta-cell function. MicroRNAs (miRNAs) are small non-coding RNAs acting as key regulators of gene expression. Here, we demonstrate that miR-101a and miR-30b are key players in cytokine-mediated beta-cell dysfunction. We found that IL-1 beta induces an increase in nniR-101a and nniR-30b in MIN6 cells, and that the two miRNAs participate in beta-cell dysfunction, including decreased insulin content, gene expression, and increased beta-cell death. miR-101a and miR-30b reduce proinsulin expression and insulin content by directly targeting the transcriptional factor Neurod1. In addition, beta-cell apoptosis mediated by miR-101a and miR-30b is associated with diminished expression level of the antiapoptotic protein Bcl2. Moreover, we show that miR-101a causes an impairment in glucose-induced insulin secretion by decreasing the expression of the transcription factor Onecut2. Taken together, our findings suggest that changes in the levels of miR-101a and miR-30b contribute to cytokine-mediated beta-cell dysfunction occurring during the development and progression of type 1 diabetes.