| First Author | Metzger DE | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 5 | Pages | 1804-16 |
| PubMed ID | 24487024 | Mgi Jnum | J:229352 |
| Mgi Id | MGI:5751657 | Doi | 10.2337/db13-0867 |
| Citation | Metzger DE, et al. (2014) Grg3/TLE3 and Grg1/TLE1 induce monohormonal pancreatic beta-cells while repressing alpha-cell functions. Diabetes 63(5):1804-16 |
| abstractText | In the pancreas, alpha- and beta-cells possess a degree of plasticity. In vitro differentiation of pluripotent cells yields mostly alpha- and polyhormonal beta-like cells, indicating a gap in understanding of how functional monohormonal beta-cells are formed and of the endogenous repressive mechanisms used to maintain beta-cell identity. We show that the corepressor Grg3 is expressed in almost all beta-cells throughout embryogenesis to adulthood. However, Grg3 is expressed in fewer nascent alpha-cells and is progressively lost from alpha-cells as endocrine cells mature into adulthood. We show that mouse Grg3(+/-) beta-cells have increased alpha-specific gene expression, and Grg3(+/-) pancreata have more alpha-cells and more polyhormonal cells, indicating that Grg3 is required for the physiologic maintenance of monohormonal beta-cell identity. Ectopic expression of Grg3 in alpha-cells represses glucagon and Arx, and the addition of Pdx1 induces Glut2 expression and glucose-responsive insulin secretion. Furthermore, we found that Grg1 is the predominant Groucho expressed in human beta-cells but acts functionally similarly to Grg3. Overall, we find that Grg3 and Grg1 establish a monohormonal beta-cell identity, and Groucho family members may be useful tools or markers for making functional beta-cells. |
