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FOXM1 acts sexually dimorphically to regulate functional β-cell mass.
FOXM1 transcription factor enhances pancreatic beta cell function and proliferation, particularly in males. Its interaction with estrogen receptor alpha may explain why women have a lower diabetes incidence.
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Area of Science:
- Endocrinology
- Molecular Biology
- Diabetes Research
Background:
- FOXM1 (Forkhead box protein M1) is a key regulator of beta-cell proliferation and insulin secretion.
- Previous studies showed activated FOXM1 (FOXM1*) increases beta-cell mass and function in male mice.
Approach:
- Investigated the role of FOXM1 in female beta cells and human islets.
- Examined the interaction between FOXM1, estrogen receptor alpha (ERα), and beta-cell function.
- Utilized mouse models with pancreas-wide ERα deletion.
Key Points:
- FOXM1* expression did not affect beta-cell proliferation or glucose tolerance in female mice.
- FOXM1* enhanced glucose-stimulated insulin secretion in male human islets but not female.
- FOXM1* rescued impaired glucose tolerance in female mice lacking ERα.
- FOXM1 and ERα binding sites overlap with other key beta-cell transcription factors.
Conclusions:
- FOXM1 exhibits sexually dimorphic regulation of beta-cell function.
- FOXM1 and ERα cooperate to regulate beta-cell function.
- This cooperation offers a potential mechanism for the lower diabetes incidence in women.