posted on 2021-05-13, 09:20authored byYin Liu, Siyuan He, Ruixue Zhou, Xueping Zhang, Shanshan Yang, Dan Deng, Caixia Zhang, Xiaoqian Yu, Yulong Chen, Zhiguang Su
Pancreatic
β-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 β-cells is poorly understood. The present study was
undertaken in a conditional knockout of Nf-ya specifically in pancreatic
β-cells (Nf-ya βKO) to define the
essential physiological role of NF-Y in β-cells. Nf-ya βKO mice exhibited glucose intolerance without changes in
insulin sensitivity. Reduced β-cell proliferation resulting in decreased β-cell
mass was observed in these mice, which was associated with disturbed actin
cytoskeleton. NF-Y-deficient β-cells also exhibited impaired insulin secretion
with a reduced Ca2+ influx in response to glucose, which was
associated
an inefficient glucose uptake into β-cells due to a decreased expression of glucose transporter 2
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 islets homeostasis and function through regulation in β-cell
proliferation, glucose uptake into β-cells, and mitochondrial energy metabolism.
Modulating NF-Y expression in β-cells may therefore offer an attractive approach
for therapeutic intervention.
Funding
This study was supported by the National Natural Science Foundation of China (No. 81770814), the Sichuan Province Science and Technology Support Program (2020YF0192), the National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Z20201010), and the Graduate Student`s Research and Innovation Fund of Sichuan University (2018YJSY118).