| First Author | Liu Y | Year | 2021 |
| Journal | Diabetes | Volume | 70 |
| Issue | 8 | Pages | 1703-1716 |
| PubMed ID | 33980692 | Mgi Jnum | J:341744 |
| Mgi Id | MGI:7398361 | Doi | 10.2337/db20-1238 |
| Citation | Liu Y, et al. (2021) Nuclear Factor-Y in Mouse Pancreatic beta-Cells Plays a Crucial Role in Glucose Homeostasis by Regulating beta-Cell Mass and Insulin Secretion. Diabetes 70(8):1703-1716 |
| abstractText | Pancreatic beta-cell mass and insulin secretion are determined by the dynamic change of transcription factor expression levels in response to altered metabolic demand. Nuclear factor-Y (NF-Y) is an evolutionarily conserved transcription factor playing critical roles in multiple cellular processes. However, the physiological role of NF-Y in pancreatic beta-cells is poorly understood. The current study was undertaken in a conditional knockout of Nf-ya specifically in pancreatic beta-cells (Nf-ya betaKO) to define the essential physiological role of NF-Y in beta-cells. Nf-ya betaKO mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced beta-cell proliferation resulting in decreased beta-cell mass was observed in these mice, which was associated with disturbed actin cytoskeleton. NF-Y-deficient beta-cells also exhibited impaired insulin secretion with a reduced Ca(2+) influx in response to glucose, which was associated with an inefficient glucose uptake into beta-cells due to a decreased expression of GLUT2 and a reduction in ATP production resulting from the disruption of mitochondrial integrity. This study is the first to show that NF-Y is critical for pancreatic islet homeostasis and function through regulation in beta-cell proliferation, glucose uptake into beta-cells, and mitochondrial energy metabolism. Modulating NF-Y expression in beta-cells may therefore offer an attractive approach for therapeutic intervention. |
