| First Author | Lee G | Year | 2019 |
| Journal | Diabetes | Volume | 68 |
| Issue | 1 | Pages | 81-94 |
| PubMed ID | 30352876 | Mgi Jnum | J:272988 |
| Mgi Id | MGI:6280837 | Doi | 10.2337/db18-0556 |
| Citation | Lee G, et al. (2019) SREBP1c-PAX4 Axis Mediates Pancreatic beta-Cell Compensatory Responses Upon Metabolic Stress. Diabetes 68(1):81-94 |
| abstractText | SREBP1c is a key transcription factor for de novo lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic beta-cells are largely unknown. In this study, we demonstrate that SREBP1c regulates beta-cell compensation under metabolic stress. SREBP1c expression level was augmented in pancreatic islets from obese and diabetic animals. In pancreatic beta-cells, SREBP1c activation promoted the expression of cell cycle genes and stimulated beta-cell proliferation through its novel target gene, PAX4 Compared with SREBP1c(+/+) mice, SREBP1c(-/-) mice showed glucose intolerance with low insulin levels. Moreover, beta-cells from SREBP1c(-/-) mice exhibited reduced capacity to proliferate and secrete insulin. Conversely, transplantation of SREBP1c-overexpressing islets restored insulin levels and relieved hyperglycemia in streptozotocin-induced diabetic animals. Collectively, these data suggest that pancreatic SREBP1c is a key player in mediating beta-cell compensatory responses in obesity. |
