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Nuclear Factor Y in Male Mouse pancreatic β-cells Plays a Crucial Role in Glucose Homeostasis by Regulating β-Cell Mass and Insulin Secretion
figure
posted on 2021-05-13, 09:20 authored by Yin Liu, Siyuan He, Ruixue Zhou, Xueping Zhang, Shanshan Yang, Dan Deng, Caixia Zhang, Xiaoqian Yu, Yulong Chen, Zhiguang SuPancreatic
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.