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Published on: January 4, 2018
Insulin regulates menin expression, cytoplasmic localization, and interaction with FOXO1
Leah Wuescher1, Kristine Angevine, Terry Hinds
1College of Medicine, Univ. of Toledo, Health Science Campus, OH, USA.
Summary
Insulin signaling regulates the menin protein, influencing its interaction with FOXO1. This interaction, mediated by Akt, impacts metabolic gene expression, particularly in the liver.
Area of Science:
- Molecular Biology
- Metabolic Regulation
- Endocrinology
Background:
- Menin, a nuclear protein, inhibits protein kinase B/Akt activity.
- Insulin signaling pathways are crucial for metabolic homeostasis.
Purpose of the Study:
- To elucidate the novel insulin-dependent regulation of menin.
- To investigate menin's interaction with metabolic proteins like FOXO1.
Main Methods:
- Time-dependent insulin exposure and receptor studies.
- Inhibition analysis using PI3K/Akt inhibitor LY-294002.
- Fasting/refeeding models and liver-specific menin deletion.
Main Results:
- Insulin downregulates menin expression and promotes its cytoplasmic localization.
- Akt is critical for menin regulation; PI3K/Akt inhibition abrogates insulin effects.
- Insulin increases menin interaction with FOXO1, particularly in the liver.
- Menin deletion in the liver upregulates FOXO1 target genes.
Conclusions:
- Menin expression and localization are modulated by insulin signaling via the Akt pathway.
- Insulin-induced menin-FOXO1 interaction has significant metabolic consequences.
- This pathway offers a new target for metabolic disease research.
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