Nuclear Factor-Y in Mouse Pancreatic ?-Cells Plays a Crucial Role in Glucose Homeostasis by Regulating ?-Cell Mass and Insulin Secretion

Pancreatic ?-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 playing critical roles multiple cellular processes. However, physiological role NF-Y pancreatic ?-cells poorly understood. The current study was undertaken a conditional knockout Nf-ya specifically (Nf-ya ?KO) define essential ?-cells. ?KO mice exhibited glucose intolerance without changes sensitivity. Reduced proliferation resulting decreased observed these mice, which associated with disturbed actin cytoskeleton. NF-Y–deficient also impaired reduced Ca2+ influx glucose, inefficient uptake into due GLUT2 reduction ATP production from disruption mitochondrial integrity. This first show that for islet homeostasis function through regulation proliferation, ?-cells, energy metabolism. Modulating may therefore offer attractive approach therapeutic intervention.