| First Author | Richards P | Year | 2018 |
| Journal | Diabetes | Volume | 67 |
| Issue | 3 | Pages | 461-472 |
| PubMed ID | 29282201 | Mgi Jnum | J:258313 |
| Mgi Id | MGI:6117901 | Doi | 10.2337/db17-0595 |
| Citation | Richards P, et al. (2018) MondoA Is an Essential Glucose-Responsive Transcription Factor in Human Pancreatic beta-Cells. Diabetes 67(3):461-472 |
| abstractText | Although the mechanisms by which glucose regulates insulin secretion from pancreatic beta-cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralog carbohydrate-responsive element-binding protein, is the predominant glucose-responsive transcription factor in human pancreatic beta-EndoC-betaH1 cells and in human islets. In high-glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes arrestin domain-containing protein 4 (ARRDC4) and thioredoxin interacting protein (TXNIP), the latter being a protein strongly linked to beta-cell dysfunction and diabetes. Importantly, increasing cAMP signaling in human beta-cells, using forskolin or the glucagon-like peptide 1 mimetic Exendin-4, inhibits the shuttling of MondoA and potently inhibits TXNIP and ARRDC4 expression. Furthermore, we demonstrate that silencing MondoA expression improves glucose uptake in EndoC-betaH1 cells. These results highlight MondoA as a novel target in beta-cells that coordinates transcriptional response to elevated glucose levels. |
