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Hepatic foxO1 acetylation is regulated by menin and influenced by insulin signaling
Author(s) -
Wuescher Leah,
Angevine Kristine,
Mensah-Osman Edith
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1110.6
Subject(s) - acetylation , foxo1 , insulin , insulin receptor , chemistry , medicine , endocrinology , microbiology and biotechnology , signal transduction , insulin resistance , biology , biochemistry , protein kinase b , gene
Objective To elucidate the relationship between hepatic menin and FoxO1 with respect to protein interaction and post‐translational modification of a metabolically relevant protein. Method NIH‐3T3 cells were stably transfected with human insulin receptor, serum starved, and protein levels were measured. HepG2 cells were serum starved and treated with 100nM insulin. Animals were fasted 18h, re‐fed 4h, 7h, and random fed. Results Menin levels were significantly decreased by 24h exposure to insulin in 3T3 cells stably transfected with the human insulin receptor, however acute effects of insulin show increases in menin mRNA expression. In the liver and HepG2 cells menin interacts with the metabolic protein FoxO1 in an insulin dependent manner. Menin siRNA results in an insulin dependent decrease in FoxO1 acetylation. Conclusions Insulin regulates menin expression both acutely and chronically in a biphasic manner. Furthermore, insulin mediates FoxO1 and menin interaction after 2h of exposure in HepG2 cells and with fasting and refeeding in C57/BLK6 mice. Loss of menin expression down‐regulate the acetylation state of FoxO1 in an insulin dependent manner. This data implicates menin in the regulation of a metabolic pathway via post‐translational modification of FoxO1 which regulates its cellular localization. Institutional Funding from the University of Toledo College of Medicine was used for these studies.