| First Author | Rachdi L | Year | 2014 |
| Journal | Cell Cycle | Volume | 13 |
| Issue | 14 | Pages | 2221-9 |
| PubMed ID | 24870561 | Mgi Jnum | J:223497 |
| Mgi Id | MGI:5649217 | Doi | 10.4161/cc.29250 |
| Citation | Rachdi L, et al. (2014) Dyrk1A induces pancreatic beta cell mass expansion and improves glucose tolerance. Cell Cycle 13(14):2221-9 |
| abstractText | Type 2 diabetes is caused by a limited capacity of insulin-producing pancreatic beta cells to increase their mass and function in response to insulin resistance. The signaling pathways that positively regulate functional beta cell mass have not been fully elucidated. DYRK1A (also called minibrain/MNB) is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. A significant amount of data implicates DYRK1A in brain growth and Down syndrome, and recent data indicate that Dyrk1A haploinsufficient mice have a low functional beta cell mass. Here we ask whether Dyrk1A upregulation could be a way to increase functional beta cell mass. We used mice overexpressing Dyrk1A under the control of its own regulatory sequences (mBACTgDyrk1A). These mice exhibit decreased glucose levels and hyperinsulinemia in the fasting state. Improved glucose tolerance is observed in these mice as early as 4 weeks of age. Upregulation of Dyrk1A in beta cells induces expansion of beta cell mass through increased proliferation and cell size. Importantly, mBACTgDyrk1A mice are protected against high-fat-diet-induced beta cell failure through increase in beta cell mass and insulin sensitivity. These studies show the crucial role of the DYRK1A pathway in the regulation of beta cell mass and carbohydrate metabolism in vivo. Activating the DYRK1A pathway could thus represent an innovative way to increase functional beta cell mass. |
