BACKGROUND The transcription factor YY1 is an important regulator for metabolic homeostasis . Activating mutations in YY1 lead to tumorigenesis of pancreatic β-cells, however, the physiological functions of YY1 in β-cells are still unknown . Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism .
METHODS We established two models of β-cell-specific YY1 knockout mice . The glucose metabolic phenotypes, β-cell mass and β-cell functions were analyzed in the mouse models . Transmission electron microscopy was used to detect the ultrastructure of β-cells . The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function . Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in β-cells .
RESULTS Our results showed that loss of YY1 resulted in reduction of insulin production, β-cell mass and glucose tolerance in mice . Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic β-cells . The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models .
CONCLUSION Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in β-cells.